in my experience the mundane archennemies are the best ones. Look at Lex Luthor or the Joker.
I would go with Rogue/Monk, lots of minions of all colours and shapes, tons of esacpe routes, magic items and traps.
He has lots of skillpoints and special abilities to be powerful and flexible, but he can't do everything.
Or if you really want to go arcane
Alchemist/Witch
Experiment with both the living and the undead, cook people, smell children, be on steroids or take mind enhancing drugs. Think Irenicus (Baldurs Gate II) meets Mengele.
Hope you're players are above 18.
Edit: go clone master+mindchemist / beast-bonded and you'll never have to worry that they can really kill him.
Or reanimator+mindchemist / Gravewalker for the ultimate undead thrill
Well, I'm more interested in a Villain with a real theme behind it, not just powerful class combos
The prior suggestions did seem to have themes behind them (quite good ones to me), but I'm guessing that they probably weren't themes you were interested in. What kind of theme does interest you? That way we can give you more directed advice that you might see more use in.
Demoniacs, good-intentioned evil, undead, tragic villains, multiple personalities, grey-moral vigilantes, twisted and insane acrobats, the unpleasant side of nature, nightmare-inducing clowns, what gets to you and your players? We can suggest a lot, but if you don't like it, it doesn't do any good.
(also note, if you are worried about PrCs in Gestalt, just do like I do and say "PrC counts as both your classes while you are taking it." They won't touch them with a ten-foot pole.)