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?
Thanos was a great villain because he had a vision and wouldn’t compromise. Granted his vision was horrific and flawed, but he held true to it.
It cannot be Thanos because he did nothing wrong.