1. Lex Luthor. I would rate him as number one because DC, Animated Series, Movies and TV, etc make him number one. Personally, I think Superman could do better only because there's so much in the way of politics when Luthor's involved.
All the others below, in no particular order (probably missed a few):
Bizarro - classic, people for some reason identify with him (more than just a superman villain, his name is synomous with odd behavior). You sometimes also feel sorry for him (depending on the story). He complements Superman because he wants to be him but he also makes a mockery of him.
Mr. Mxyzptlk - because there is something really cool to having the powers he has but being constrained by rules. Mixy is imagination and impishness unleashed. When he's around, everything gets very interesting. He's just fun to watch.
Cyborg Superman - if there was an evil superman, this is him. Maniacal, power-hungry, no problems with killing. He's the one guy Supes has to take down... hard!
Metallo - because of his morphing capabilities, incredible strength, cold heart and ability to manipulate other mechanical devices - makes a great villian for superman and someone who creates alot of problems.
Brainiac - smart villians stay around longer than brute strength villians. They always find ways (tech, chemistry, master plans, etc) to fight and survive. The brightest of these sometimes develope cult followings because they bring so much to the table. This epitomizes Braniac who not only stays around but whose offsprings also become major players.
1. The Joker - killing Robin and sending Batgirl to a wheelchair cemented his position as the number one Batman villian.
All the others below are unsorted - tried to stay away from the crazies (as they don't really appeal to me personally).
Ra's al Ghul - in many ways, Batman's true mental counterpart. He's batman without getting his hands dirty.
Prof. Hugo Strange - although this character has been around since forever, his stock is rising once again. Brilliant scientist with so many different ways to attack.
Deathstroke - He's become very popular (like deadpool) and displays the kind of killer instincts of anti-heroes like wolverine and the punisher. DC may be forced to make his role vague (in the grand scheme of things - a gray area villain, gray area hero...). Who's the better fighter, DeathStroke or Batman? Who's the better strategist? We may never know... perfect Batman counterpart.
Lady Shiva - in many ways, represents the new wave of villains that are making strides within DC. Batman used to have alot of crazies. Now he's dealing with the fighting elite, trained warriors, tacticians. And not all of them are men.
Bane - the guy broke Batman's back. Nobody will ever let you forget that. This remains his crowning achievement. Batman wasn't just beaten, he was crippled. Since May of 1939 (when batman first appeared), villians have been trying to break him. Bane did it physically. The Joker nearly succeeded on an emotional level. For Batman, this is personal...