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?
As a super Dune nerd, Erasmus.
From DC: Larfleeze and Volthoom tied. Oh! The Anti-Monitor too.
From Supernatural (the TV series), Crowley is amazing.
BSG: Dr. Gaius Baltar.
the show did crowley dirty in last few seasons.