The folks behind the Batman animated series of the 90s did a lot of great things, but one of the best was the creation of Harley Quinn. Dr. Harleen Quinzel was a young psychiatrist at Arkham Asylum who was manipulated by the Joker into letting him escape. She was so charmed by him (and she's also crazy) that she got herself a harlequin costume and decided to be a sidekick to the Joker (who she refers to as either "Puddin" or "Mr. J."). The Joker doesn't really want her around, but once in a while he finds her useful, and shows her enough kindness to get her to do what he wants. Which is usually enough to keep her completely infatuated with him.
Harley was introduced into the comics universe later and was just as successful there, most notably in the Eisner Award winning Mad Love. She's grown a bit beyond just being Joker's sidekick, having bonded with Poison Ivy, worked on her own, and even joined a team of villains.
Pros: Her costume, often accompanied by a comically oversized wooden mallet, is a crowd pleaser. She's a very popular character in general and can be a whole lot of fun.
Cons: So much of her identity is tied in with the Joker, and Heath Ledger's performance was too brilliant, and his death too tragic, for anyone else to play the part. And even so, Harley Quinn fits in a more kid-friendly, comical Gotham City, where the Joker has a flower on his lapel that sprays crazy purple knockout gas, or he carries a gun that shoots out a flag that says "Bang!"
How I'd do it: Like Calendar Man, but for a different reason, I just wouldn't do it. If the Joker could come back, one could easily tell Harley's origin, starting the movie with Harleen examining the Joker in Arkham and run from there, but even then she might just be too comical for the tone they've set in the movies.
Casting Guesses: Kristen Bell can do bubbly, Britney Murphy can do crazy, Scarlett Johansson can fill out the costume nicely and she's a good enough actor that she can do something with the part. Either of the three would be fine. Anna Farris might be the best choice though.
Verdict: No. Can't do Harley without her Puddin', and I'm not sure they'd want to anyway.
After The Scarecrow, Ra's Al Ghul, The Joker, and Two-Face, who should be Batman's next enemy in the Batman Begins/The Dark Knight series? Well, as of now we know that Tom Hardy will play Bane and Anne Hathaway will play Catwoman.
Check out the master list for all the villains covered. I've pretty much run out by now. Obviously, there are more Batman villains, but not any of significance that I know of. As of February 2009, no one is confirmed as a villain. Not the Johnny Depp Riddler, not Phillip Seymour Hoffman Penguin, nobody.