That largely depends on how you rank them. In order to get away from the creeping terror preying upon my mind right now, I'll write a long post about it.
Power
*Note: I do not know the capabilities of the villains of any Final Fantasy before VI, so I won't be including them.
This almost certainly falls to Lavos; the potentially strongest antagonist, Ultimecia, never gave us anything but her word that she was actually capable of assimilating the universe, and her effectiveness against Squall doesn't seem to hold up notions of her success. By contrast, Lavos himself is actually seen to have caused the K-T extinction event. We don't know how much damage he sustained in the process, but it seems relatively clear that no Final Fantasy antagonist in any form demonstrated onscreen could stand up to him, unless they managed to devise the same tactics that Crono's team used, and even then it's debatable. Deus, a dedicated planetary assault machine, probably comes in somewhere near the top. Kuja and Kefka actually fall to the bottom of the list; contrary to the claims of his fanboys, the World of Ruin was in no way, shape, or form effected under Kefka's own power. The World of Ruin was the sole creation of the imbalance of the Statues' power, and the Light of Judgment is never demonstrated to have such pervasive effects. In fact, its use is invariably quantified as vaporizing towns. By the end, Kefka is stated to have absorbed the full power of the Statues, but this is not demonstrated. This is no more effective than an average tactical nuke, and probably even less so considering the medieval-scale towns of FFVI's world. Kuja was also never demonstrated to actually have pulled an Alderaan on Terra. Instead, he destroyed all planetary structures in an unknown radius not by directly attacking them, but by sniping at their foundations, which any engineer would be hanged for designing. It could have been anywhere from the immediate area, which makes him about as effective as Kefka, to all the structures on the planet, which places him somewhere between Kefka and Sephiroth after taking a Lifestream bath.
In terms of potential, it again falls to Lavos. Chrono Cross' storyline literally cannot happen without the claims of his potential universe-consuming power being true; they're even backed by Belthasar, one of the most brilliant scientists and engineers who ever lived. Sephiroth has the potential to be one of the more powerful antagonists; his potential could range anywhere from planet-busting to actually being able to cause a supernova (the Super Nova attack is generally not taken as canon). Conceivably, Kefka would be next; if he did actually manage to absorb the Statues' power, he'd have abilities several times more powerful than those of Sin, whose power is a fixed entity right from the start. Kuja probably can't get much more powerful than he was at the end of FFIX; he was relying on a deus ex machina to destroy the multiverse.
Success
Lavos undoubtedly is the most successful. At any point when time travel is required to deal with the main villain, he's simply too strong to be comparable with villains who aren't in the same class. I would put Kefka next, since he's the only other villain that's succeeded for any measure of time with his primary goal. He isn't too powerful on analysis, but with the Statues having wrecked the world for him, he doesn't have to be. All that matters is that he's strong enough to be unassailable by anyone he's oppressing. For all of Sephiroth's hype, he doesn't actually achieve much success. He does succeed in crashing the world economy and probably killing a bunch of people, but economies can be rebuilt, and the number of people lost was not a major catastrophe on a global scale. Kuja was actually a failed experiment, so he can be said to be the weakest in terms of success; the only thing he really succeeded in doing was getting some people killed, without bringing about the kind of total war necessary for Darth Garland's pet project.
Impact
This is a completely subjective matter; it's almost impossible to definitively identify the best antagonist for a story perspective, since virtually all of them symbolize completely different traits and themes. Sephiroth is certainly the most iconic; other than Lavos, he's the only Square villain I know of who returned as the villain in a dedicated sequel, but popularity alone does not a good villain make. He's one of my personal Jeebuses, but I can't speak for everyone.
