Top antagonists for me were Sepiroth from Final Fantasy 7, Seifer from Final Fantasy 8, and probably Tyrant and Nemesis from the Resident Evil series. Sepiroth was classic, and the back story that FF7 chronicles makes the gamer understand his hatred and how his villainy manifested. Bonus points for the end game battle with Sepiroth being one of the best battles in gaming history (IMO). Seifer was cool because he had been rivals with Squall from Balamb Gardens towards the last boss encounter. The ominous music that would play right before Nemesis or Tyrant would bust through a wall used to scare the crap out of me.