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?
Shepard Lambert in Would You Rather?, played by Jeffrey Combs.
Picking a Jeffrey Combs role is cheating though.
Okay, fine. Monster (2004)'s Johan Liebert.