The first thing before I start is to define what a villain is. A villain is not just someone who oppose the hero. He is a despicable being that the hero (or in case of videogames, the player controlling the hero), despise with all his/her/its heart. A villain have, in the eyes of the hero/player, no redeeming qualities, no chance of redemption and no reason to not be killed in gruesome manner.
An antagonist, in the other hand, is just someone who opposes the hero/player. It can be someone as good as the hero, but with a conflicting objective. For example, you may want to get a criminal, while the antagonist, knowing this so-called criminal is innocent tries to avoid you to do it.
With that in mind, the greatest, evil-est villain I ever met in games must be Kefka from Final Fantasy VI. He is evil incarnated. He (spoilers ahead) poison the water source of a castle killing most of their inhabitants and even Kefka's own soldiers; he kills his boss; and destroy the world! Yes, he was able to destroy the world before the heroes could stop him, becoming the ruler of whatever remained. The rest of the game puts you trying to find the remaining allies and trying to remake the world. Killing Kefka, of course.
What made Kefka such a remarkable villain is that he is not likable at all. He does not have a tragic past which the players/heroes can pity him for, he is not moving by a righteous desire but with not so righteous ways to do it or even being a goofy, comedic kind of villain so we can laugh at him. No, he was the most classic kind of villain I ever met. Damn, he is such a douche bag that there is no one wanting to be like Kefka, while some villains have true fans!
Today we have more antagonists than villains (from the serious, good games) or outright ridiculous funny villains (from less serious or less good games). True villains are a rarity in my eyes and sometimes I miss this kind of really evil, nobody loves him/her/it kind of villain.