Mewtwo is THE ultimate super-boss.
If you don't believe it, then try to beat him on the Pokemon Stadium games. I guarantee that it won't be pretty.
Since he also happen to be the big bad final boss of most of the non RPG games, he also happen to be the most recurring one and as such, reached "classic final battle" status in my book. Surprisingly, my favorite version of the big bad genetic abomination is not his Pokemon Stadium one but the Puzzle League one... although if Mysterious Dungeon gets released in english and that I get to face him, my opinion could change... [SPOIL]According to guides, Rayquaza is the first, normal final boss. Mewtwo awaits at the end of the true final dungeon. I expect him to be just as fiendishly hard as usual. As a bonus, it may also seems that beating him (thus beating the game for real) unlock a "boss rush" of sort... in short, all bosses revive in already-beaten dungeons and can be fought again (useful for those bosses who did not join the party when beaten the first time... getting the normal final boss in your party, anyone?).[/SPOIL]
Ash Ketchum/Red from Gold/Silver/Crystal get close second.
You get to defeat the hero of the anime (and pretty much the emblem of Pokemon) so for both anime fans and haters, that's a plus.
Furthermore, face it. His Pikachu and his Snorlax are pure, sheer evil.
My third vote goes to Steven. I thought that he was actually the most decent Champion although the fact that he's rather lame for a final boss because of his lower levels... especially considering how fiendishly hard was the final boss of the last generation of games (Ash, who else?).
Well, that's that.