What are some notable blunders in history that resulted in huge loss?

I'm willing to nominate Charles II, King of Spain as a formerly alive blunder. The result of decades of Hapsburg inbreeding, he had a number of health and intellectual issues from birth and he was notably infertile. If you live in a monarchy where succession is passed down through children, it's REALLY BAD to be infertile and be King. His death directly caused the War of the Spanish Succession, a 13-and-a-half year war that eventually involved pretty much all of western Europe and likely led to the deaths of over 1 million people.

Literally could have avoided this if the Habsburgs decided to have sex with other people.