With word that the title of the new Batman movie is "The Dark Knight Rises" and the villain won't be the Riddler...
Browsing Wikipedia, I had an impromptu brainstorming session regarding Christopher Nolan's Batman universe.
Some Batman villains could be tweaked just a bit to make them fit into the realistic world. Others require a bit more origin mixing around to fit in, but could work.
So, let's get right into it and go villain by villain and theorize how they'd fit in Nolan's world.
Bane - Gets super strength from a drug called Venom. Makes his muscles grow to monster sizes. Some real drugs like PCP can make users a bit crazy with what seems like unusual strength and feeling no pain. Playing off that would be easy and could make for a scary villain.
Clayface - Radioactive material turned the second Clayface into a monster who could take any form and mostly appeared as a monster made of clay. The first Clayface was actually a normal guy.
He was an actor who went crazy and started killing people. An easy realistic approach could be to have Clayface be a master of disguise. He could be an actor who's family or loved one was killed by something in the first two films and he blames Batman.
Mr. Freeze - Was a scientist who had to live in subzero temperatures. He also used various weapons to freeze people. The only real realistic approach would be to make him some sort of serial killer who uses liquid nitrogen to kill people.
Penguin - This one is an easy fix. Just get a small fat guy who has an umbrella fixation. Just give him an umbrella gun and an umbrella sword. Make him the new mob boss of Gotham.