Kahn is obviously the number 1 villian, Shinzon tried but failed to fill his shoes for TNG. I cannot help but find it amusing that Kirk's ultimate enemy was a genetically enhanced superbeing, while Picard's was a defective clone of himself. Shinzon did manage to prove that Picard was his own worst enemy.
The Romulan Commander from the TOS episode "Balance of Terror" is also an excellent villian.
Garth of Izar from the TOS episode "Whom Gods Destroy" is probably one of the most underapreciated villians.
Trelane from the TOS episode "The Squire of Gothos" was very memorable, so memorable Q was an obvious homage to him.
Koloth, Kang, and Kor were most excellent foils.
Nomad from the TOS episode "The Changeling" was so awesome that he was rehashed as V'Ger in the Motion Picture.
The Borg Queen from First Contact, is the best TNG ever did, and they had to break all established canon to do it.
Lore was a good villian.
Gul Madred from TNG episode "Chain of Command"
Roga Danar from the TNG episode "The Hunted" was an entertaining adversary, though not trully a villian.
The baddies from TNG episode "Conspiracy" had great potential, but were never fully developed.
Shran is not a villian.
My favorite "villians" in any variant of Star Trek were never people but, rather, the intangibles. Prejudice, fear, ignorance, arrogance. My favorite episodes were the ones where THESE were the primary adversaries to be vanquished. That's what I feel became increasingly absent in the series (both TV and Movies) as it progressed. That's what I would MOST like to see a return to both in the series and in STO. And the wonderful thing about intangibles is they can come back again and again and again with no need to invent some stupid resurrection plot heheheheh :p