This is a conventional pick, but GlaDOS from Portal has to be the best antagonist. GLados (Genetic Lifeform and Disk Operating System) is a central core that is suppose to control the “the Aperture Science computer-aided Enrichment Center.” She is a major narcissist. Her consciousness had been controlled “by personality cores.” GLaDOS is one of the most memorable villains in gaming.
Despite being a villain, she made the game entertaining. In particular her wit, passive aggressive attitude and sarcasm are enjoyable. You need her to progress through the game, even though you can’t really trust her. GLaDOS manages to be both a threat and a delight. At the end of the day, who doesn’t want to play against an rude, funny and homicidal AI.