Who is the cruelest fictional villain?

God.
- Give it a rest, kiddo.

First thought is that its almost certainly something from Warhammer 40k. Probably one of the Dark Eldar (or just their civilization as a whole). They're a super-advanced, post-scarcity civilization that basically worships torture and uses their technology to "perfect" it.
Edit: spelling
- Or Erebus, because fuck him.
- Ford Prefect?
- Na, the C'Tan is the cruelest. You Necrons want to be free of cancer riddles bodies we caused by consuming your sun and become immortality? Sure, here is a metal container for your brain while we consume your essence because it taste better than solar winds.
  Got what they deserved though.

There was an old Captain America comic where the Red Skull had a glass floor in his dining room so he could look down on the torture chamber underneath.

Having played the evil path in Star Wars KOTOR.. I'd have to say it's me.

Ramsay Bolton did a lot of skinning. So much skinning.
- Wiggles sausage suggestively

The reverse flash . Goes back in time to kill the flashs mom just because he hates the flash and to inflict as much emotional damage as possible.

Anubis from SG1. Dude was banished by the other goa’uld for doing unspeakable things.
- I disagree… but you’re close.. the ancients.
  Not only do they see all the horror and suffering that Anubis and the goa’uld inflicted on the universe; the could have done anything… not even helping; rather they never even hindered Anubis
  
  They didnt do shit until he halfway ascended and became a threat to them. And how did he halfway ascend? Oma fucking Desala meddled with the mortals, again. And when a mortal gave up everlasting life and power to un-fuck their mistake, they un-ascended him!
  They really took a nosedive in the public relations there.
- And kind of a dick about it, too.

The Crippled God from Mazalan Book of the Fallen. I should probably spoiler this. And trigger warning.
- How is this series? I only glanced at the spoiler but some of the last bit was...a lot. Do most of the books receive that trigger warning or is that more of a endgame thing?
  
  As Llamapacolypse said, it has it's dark moments. What I wrote above is some of the darkest. It never goes into too much detail when it involves some of the more triggering things. Just a fade to black.
  That said it's such an intensely human series. So much love and compassion litered throughout the whole thing.
  It's also such a unique experience. Most fantasy books have huge massive reveals that shock and take you by surprise. Malazan has these things. But it also does it in reverse. You'll read something and then a book or two later it changes context entirely, completely blowing your mind.
  
  The series is fantastic but it does get quite heavy in a lot of ways. Very heavy on the ways people and societies are shitty to each other, but the central theme of it really is compassion.
- Glad to read about Malazan 😊 here

C'Tan from 40K
Causes the Necrons to be a short lived race because the C'Tan living in their sun. A series of wars happen and the C'Tan is like "oh hi, we can make you 'immortal'"
Turns the civilisation of Necrons into the slave machine race we know in 40K
- The worst part was, the C'tan which ended up being known as The Deceiver convinced them that they could make the Necrontyr immortal, fixing their cancer ridden short lives, and aid them in their war against the Old ones. This was accomplished by a process called bio-transference using the bio furnaces. As the Necrontyr either willingly or unwillingly lined up to burn up their bodes in the furnaces, the C'tan could be seen above the bio furnaces gorging on the souls of the Necrontyr burning.
  Yeah, fuck those things.

The Shapeshifters from Deep Space 9. They put a pox on an entire race for being disobedient.
- I was gonna say that alien from TNG who wiped out an entire civilization because they killed his wife.
  
  This is a very interesting thought: the Dowdy alien you mention has wiped out an entire race of 50 billion beings, but is aware of his crime and lives in self exile. He's committed an atrocious crime in a rage fit.
  On the other hand, the changelings committed a planned crime with intent to cause suffering.
  I'm not sure who's worse: the Dowd by magnitude of the crime, but the Changelings ruthlessly command their Dominion.
  
  Or the guy from Voyager who erased multiple species from ever having existed in a misguided attempt to resurrect his family.
- Which aliens got the po?
  
  I dont remember the name of the episode, but Bashir took a leave of absence and hung out on this planet for, I'd guess, a year to work on a cure. He didn't find a cure but managed (by accident) to make a vaccine that saved new-borns from getting infected.

Kefka from Final Fantasy VI, Majora's Mask from Majora's Mask, or AM from I Have no Mouth and I Must Scream are all pretty evil.

The Fleshmancer in Sea of Stars is pretty terrible. He creates giant, potentially world destroying, monsters that feed on different types of despair, and so seek to create those emotions in as many people as possible. He committed one genocide against an entire race, and then trapped them in living death, unable to be seen, or leave his lab. He seems to have committed another genocide, just to make a birthday present for his friend. And this is all on just two planets, when he is acting in the same way across the entire multiverse

Naraku from Inuyasha.
Oh wait no.
God from The Bible.
- I don't remember all that much about Inuyasha but I remember while watching it thinking I had never hated a villain so much in any other thing I'd seen

Big Brother.
The paranoia of everyone being on the watch for everything forcing everyone to be even more paranoid
- It was even more insidious than that. It wasn't about self-preservation or selfish need... they were so brainwashed they considered it good to tell on others as a matter of course. One of the secondary characters is even proud of his own children for turning him in for talking in his sleep.

Delores Umbridge.

Semirhage from the Wheel of Time. She was a torture specialist who would use the one power and her knowledge as a top healer of the body and mind to use both pain and pleasure to turn her victims to the dark or send them to attack their loved ones. She was effective enough that they tended to either succeed or fail because they were found out, rather than the person deciding against it once they were free. Even those who had turned and were restored using age of Legends mind restoration techniques lived in constant fear of ever being in her hands again. They had to take special precautions to prevent prisoners from committing suicide after finding out they were being put in her charge. She was a sadist who would cause unnecessary levels of pain during her healing even before the bore was drilled and joined the dark because she was caught and offered the choice of oath rod vs violence or being severed from the source.
Though some of the other Forsaken give her a run for her money.
Graendal with her mind slaves that she would use for pleasure or just furniture.
Sammael who, when told that he was giving his prisoners of war half the food they needed to survive, immediately ordered half to be executed (and generally just fed them to the trollocs even when they had enough food).
Aginor who joined the shadow because they wouldn't let him do the experimentation on animals and people that he wanted to. He then created the trollocs and other shadowspawn and took 10k people per day for experiments and fodder from the start of the war power to the end of it, potentially doubling that number in the last 5 years of it.
Moghedian who ran evil schools that had children at first informing on their loved ones and later carrying out their executions themselves. During the breaking of the world, these children caused chaos that seemed like they were racing against male channellers going mad to break the world.
Balthamel established breeding camps for humans to be fed to trollocs. He also had a temper that almost got him oath rodded before the war of power.
Plus just general genocide, terror, manipulation, war, and oppression by all 13 of them. These ones stand out a bit more in their cruelty. Ishamael ultimately didn't want to be reborn anymore, Lanfear was obsessed with Lews Therin, Asmodean wanted to live forever and be a well known composer. Demandred, Be'lal, and Rhavin were jealous of Lews Therin's success. Mesaana wanted to be a researcher. They all did evil shit and didn't care about the people they hurt, but the ones in paragraphs above seemed to do it as the ends, rather than a means to an end.
- Oh yeah, extra tidbit about Semirhage: she discovered that 13 channellers and 13 myddraal could be used to turn a channeller without torture required. But she preferred the torture way.

Se7en.
One of the few onscreen villains that gave me nausea.

The fella from Old Boy.

My guess is gonna be a Dr. Who or a Black Mirror villain that utilized deep psychological horror. Maybe one of the ones that made people into immortals or data-immortals with a near infinite amount of time combined with horrifying living conditions to break their victims.
Or Hades/other Greek gods and such.
- The Mistress resurrected the dead all throughout earth and created paradise to turn them all into cybermen, android with a chip to prevent emotions, if that chip gets removed cybermen go into an agonizing pain due to realizing what they have become
- Doctor Who (him/her)self has done so many messed up stuff in the name of his/her own moral compass.
  
  But it was her mother who destroyed half the universe.
- Hades is far from being evil. He's a loyal husband and impartial/ fair when dealing with the dead. He even did a solid for Orpheus that one time and all. Too bad homie didn't follow Hades' clear instructions.
  Zeus on the other hand.... Yeah...

You could really take your pick of Vampire the Masquerade baddies.
Ur-Shulgi, for instance, who looks like a charred corpse, has led multiple genocides, is directly referred to as "violence incarnate," and doesn't seem to have a goal beyond exterminating everything he considers unclean. Depending on who you ask, that may very well be damn near everything, period.
Or Sascha Vykos, who... to call them a torturer is like saying Michelangelo kinda knew how to paint. Vykos is a monster in every sense of the word, and cruelty is both method and goal in a lot of their schemes.

The Endsinger is up there. FFXIV Endwalker spoilers follow. ::: spoiler spoiler She was tasked with finding the meaning of life, but the vast indifference of the universe turned her into the incarnation of depression. She determined that life is pointless and invariably leads to suffering, and decided to end all life in the universe as a kindness. She made her nest at the edge of creation, where she gathered all of the souls of the dead to prevent their reincarnation and feed on their despair and suffering, to eventually grow powerful enough to accelerate entropy and bring about the heat death of the universe.
She was defeated by the power of friendship. And our best frenemy.
:::
On second thought, Valens van Varro is worse. Fuck that guy.
- I wouldn't call her cruel. Misguided? Sure. Megalomaniacal? To a degree. But not cruel. As you say, she considered it a kindness.
  
  She literally recreated civilizations from the souls of the dead at the height of their suffering to harvest their negativ effects on dynamis.

From the TV adaptation of Asimov's Foundation
Cleon XIII: Orders the deaths of 1551 innocent people to make an example of one person.
Cleon XVI: Oversees the destruction of the Foundation in truly spectacular fashion.

I will always say Fuck Makima
Chainsaw Man

The witch from the witches house game. I won't spoil it here but the second ending is really hearty breaking and cruel, I recommend you watch a playthrough of the game.

Let's see, the joker? No. Golb? No. Bill cypher? Good choice, but no. As stupid as this answer might be, for me, it's most likely homelander from the boys. Homeland is established to be a cruel, terrifying, and sociopathic villain who doesn't care about who lives or dies, and all though that can be said about the ither villans I had listed, homelander is diffrent. For an example, the joker kidnapped Jason Todd, tortures him, and became the ultimate reason red hood even kills, but homelander doesn't kill people to hurt someone else, he just kills because he likes it. The joker does everything he does to get closer to batman to mess with him, but homelander just wants to see blood. Another example, Bill Cypher torments Ford and uses the people of gravity falls as his puppets, but he does that because he felt restricted by his realms 2 dimensions and wanted to be a God. Homelander thinks he is God, and thus believes he can just do anything he wants, a decides not to commit mass genocide, but torment people one at a time and either convince them to kill themselves or kills them because he's done toying with them.

Salem from RWBY