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?
An old one, but the Emperor from Gladiator. His death is among the most satisfying in movie history. Absolutely amazing performance by Joaquin Phoenix.