For me, it would be GLaDOS.
Portal 2 spoiler
She deleted the one remaining human part of herself because it was just too much to deal with. She releases you at the end of Portal 2 as a path of least resistance measure because “killing you is hard.”
What about you, what is your favorite media villain?
Megamind was the first thing that popped to my mind without thinking further. Was hoping someone said it, didn’t have to scroll that far either.