Matt and I were discussing possible previously-unused, non-supernatural Batman villains that might fill the role in The Dark Knight Rises. I didn't have a list off the top of my head at the time, but here are a few more that might fit the bill:
Hugo Strange - This was one that Matt and I were talking about originally--he brought him up. Strange was one of Batman's original villains, the caretaker of Arkham Asylum and, eventually, a wackjob himself. Strange might be an interesting choice, though there's some degree of overlap into Scarecrow territory, but being one of only a handful of villains to learn Batman's secret identity, Strange is a wary foe plot-wise. Still, he was the (semi) main villain for two of my favorite episodes of The Batman cartoon reboot: Gotham's Ultimate Criminal Mastermind and Strange New World (the latter of the two I cannot recommend enough). Strange is apparently the current, rumored top contender (partially due to the Batman: Arkham City reveal trailer, but lets not let IMDb scuttlebutt damper our investigative curiosity, shall we?
Victor Zsasz - This guy had a cameo at the very beginning of Arkham Asylum. He's a serial killer in the DC canon, cutting scars into his body with every kill. He's certainly dark enough to fit the bill for Nolan's Batman saga, but his body count doesn't really match what previous villains have been capable of, and after offing most of Batman/Wayne's friends in The Dark Knight, taking a single damsel in distress hostage just doesn't seem viable.
Killer Croc - Again, a solo killer, but with the muscle to take out the trash. Crock is technically already part of Nolan's series--he appeared as a villain in the animated direct-to-DVD animation compilation (which was actually quite good) that was released to promote The Dark Knight. This guy's issue, though, is not so much about quantity of threat as intelligence. He's dumb. Like, real dumb. Hardly the sort of thing that Nolan's detective would waste his time on, and not really the kind of fodder for big explosions either--he's more of a water kind of guy.
Toyman - Again, the serial killer type, though this guy has the chops to take out swaths with his antics. As the Batman series has progressed, Toyman has drifted from humanity and, in several adaptations, it has been hypothesized that he isn't even human at all, which might put a damper on his being interpreted for Nolan's Gotham City. Then again, Rash Al Ghul was an immortal, so maybe fudging a little here and there isn't that big of an issue.
Ventriloquist - This guy has also been a pretty prominent staple of the Batman franchise--a B-lister in terms of when the cartoon studios usually decide to brush the dust off of his shelf, but nonetheless he has connections to the crime syndicate, and taking liberties with just what his modus operandi is might make for some interesting sleuthing as to tracking down the man behind the crimes.
Black Mask - What? Marvel already HAS a Red Skull? Well, then... uh... Here's... Black Mask! Yeah! Another crime lord type, he was most recently featured in the (also quite good) Behind the Red Hood DVD release. Not as scheming or internally troubled as Ventriloquist, however--he tended to be more of the rough neck and murderous type. Plus, plenty of opportunity for more weird special effects magic.
The Joker - Well, lets face it--Nolan was talking about liking The Joker for the next film originally, and there's been no mention made about nixing that strategy, and who can blame him? Moxy, charisma, murderous intent; The Joker has it all. And, to avoid making a joke about big clown shoes to fill, it's a character actor's dream job: Chew the scenery all you want and cash in on a multi-million dollar franchise. Nolan will have his pick of the litter if he brings back the white, green, and red all over.