I've got one. Heavy spoilers are on the way for a 14+ year old game, by the way. Just warning you.
Final Fantasy VI - Kefka Triumphant
In recent year, it has come to be that far too many people consider Final Fantasy VII to be the shining moment of the series, and thus, for Sephiroth to be the best of the main villains in that game. In my humble opinion, this is fairly flawed, especially if we're going to be talking about main villains. In that case, Kefka would be the superior one. Let's take a look at Sephiroth and Kefka for a moment, to make this case.
Round One - Mass Destruction Challenge:
Sephiroth - Burns a village, leaving two (technically three) survivors.
Kefka - Poisons the water supply of an ENTIRE KINGDOM, leaving only one survivor.
Winner - Kefka
Round Two - Important Kills:
Sephiroth - Kills the head of a company you were fighting anyway, the population of your hometown, a giant snake, a bunch of his own clones, and then
Spoiler Below Aeris/Aerith/one of the girls who found Cloud attractive for God knows what reason
.
Kefka - Indirectly, he kills the lost love of one of the main characters and the father figure of a main character. Alright, now that we've got the indirect out of the way, lets get to his direct kills:
-The entire kingdom of Doma, minus one
-An entire magical race
-General Leo, one of the few good men of the Empire Kefka "served"
-The Emperor he himself swore fealty too, who he kills by tricking the Emperor into the proximity where he can be attacked by three god-like beings that now respond to Kefka's command. After weakening him, Kefka then jumps on the Emperor's neck to break it and then kicks him off of the Floating Continent, which is several thousand miles in the sky.
- And the last kill that bears discussing will be talked more in Round Three.
Winner - Kefka
Round Three - Standing Up To Heroes:
Sephiroth - Manipulates the heroes fairly well for awhile, including tricking the main character into bringing him the item he needs to summon a world-destroyer. Unfortunately for him, as most stories go, the heroes eventually come back and defeat him before his plan can come to fruition.
Kefka - See, here's where things in Final Fantasy VI get interesting. Most of the time, the climax of the game is where the villain shows his whole "here's how I'll rule/destroy the world plan, mwahahahaha" schtick, and the heroes come and defeat him. Ultimately, while the villain looks like he might win, the heroes stop him.
That's not how it works in FF VI though. You see, Kefka DOES win.
He reaches what he needs in order to summon a catastrophe, but instead of the heroes stopping him, the simply delay him for a short while. While the heroes escape death, Kefka still successfully destroys the world and ascends to godhood over the World of Ruin he's created, where he simply starts picking off the survivors of humanity at his leisure. Now, while some other stories will let the villain have an upper hand like this, it'll only be for a short while. Kefka, however, manages to maintain his position of power for a year before the heroes can regroup and stop his second stage of plans, which is to simply level the planet as a form of memorial to the idea of nihilism. On top of this, Kefka even has a cult formed around him, who worship him both out of fear and respect, desire for power, and pleading not to be killed by him.
For how moody and (honestly, to a degree) melodramatic Final Fantasy VII was, Final Fantasy VI honestly overshadowed it in a sense of well-done bleakness. That, and the fact that the villain wins the first time you REALLY need to stop him, is a hard hitting sequence in video game history.
So, third round Winner - Kefka.
Oh, and Kefka also has an awesome theme:
http://www.youtube.com/watch?v=EmmZyTwVVqY
And, in my opinion, the final boss music for the fight with him in his four staged god form at the end of the game blows FF VII's "One-Winged Angel" out of the water:
Part One -
http://www.youtube.com/watch?v=ios6zLDR8AI
Part Two -
http://www.youtube.com/watch?v=-MRGt_PvyT8
Black Mages' Cover Part One -
http://www.youtube.com/watch?v=id6PMJx31Uc
Black Mages' Cover Part Two -
http://www.youtube.com/watch?v=U_k_hWln9Xk
Yeah, okay, I guess the moment I was talking about wasn't so much the fact that Kefka won, but just how awesome a villain Kefka himself was. Still, I felt it needed to be said, since it can't be said enough.
Shine on you crazy diamond.
P.S.: Don't think I was intentionally poo-pooing Sephiroth. While he was a great villain in his own right, and VII a great game, I just have a naturally preference for VI, even though VII was the first FF I ever played.