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?
Warhammer 40k has too many good options to list. The entire ork faction is great, although one of my personal favorites is Grizgutz, an ork who accidentally travelled back in time, and decided to kill himself to steal an extra copy of his favorite gun. The Necrons are also fun, for their unlimited capacity for arrogance and pettiness.
I always liked Abbadon myself