As a player, the best villain I've encountered was a ragewalker in a game of 3e D&D, which became our Obmi. It had no backstory, no reason for being where it was, not even a name, but was a very successful villain simply because it defeated us twice in two epic battles before we finally killed it. I regarded it as the major nemesis of the campaign even though it had no relevance to the plot, it had just been a monster guarding some treasure. Not even important treasure.
I also liked a supervillain called Ruffle from a Champions game who appeared only once and got shot before she'd even had a go. Based on the name I assume she had the power to turn your clothes against you, which I thought was a rather cool and unusual concept.
As a GM -
Zeno the Super-Gorilla:
Radioactive green gorilla. Silver Age foe of the New York Five, with all their powers. By the modern age, this ex-con was a drunk, working dead-end low-level jobs in the entertainment industry in LA. He was an intellectual, I pictured him somewhat like Frasier. The PCs encountered him attempting to destroy the Hollywood sign when his powers returned. They decided to let him go after giving him a 'straighten up and fly right' speech. He did, indeed, straighten up and made a new life for himself on Monster Island.
Grackle:
A supervillain whose only power was a winged suit. He was killed by one of the PCs in his first encounter with them and later returned as a ghost to wreak his horrible vengeance. He was, again, unsuccessful.
Wrath:
Hydra-like organisation following a twisted monotheistic religion, according to which the world is, in the eyes of God, unholy, and must be destroyed. Hi-tech terrorists with a medieval flavor to their equipment, unit names and beliefs.
Sekhmet and her Super-Cats:
Feline controlling animal rights extremist who used the offspring of a silver age superpet, Ralph the Tornado Cat, as her terror weapons.
Jaditheris and the Lightning Men:
Golden Age witch of the skies. Her cloud kingdom, monsterising ray and lightning formula were discovered by CIA agents ferrying drugs in a light aircraft. The agents went rogue and cut a deal with her to take over a Central American nation.
Here, I liked the juxtaposition of golden age and modern age elements. In superhero, the combination of real world + comic book-y is often a winning formula.