Myself and a mate were debating this the other night.
My fear was that replacing Ledger would be a mistake, and something I suspect Nolan would never do. So, given that there are very few characters left in the Batman 'universe' that fit into this whole more-realistic-world Nolan's crafted, what would you do?
Personally, I think the set up for Batman being on the run from the police was great. Have him start out a fan of (some of) the people, but a foe of the police. The main villain would be the penguin (Philip Seymour Hoffman?), but he's actually an aristocratic arms dealer supplying the police with powerful arms. Gordon doesn't trust him however, and has to work closely with Batman in secret to bring him to justice. I quite like the thought of Crane reappearing too as the Penguin's right hand, undercover man, but the real villain would be the system trying to stop Gotham improving and Batman's inner turmoil (something that could be better explored I think).
It'd allow us to see more of Wayne working at his company and becoming a more fleshed out, likable social character. It could be similar in tone to the more political aspects of The Wire perhaps, but obviously with a kick ass amount of action sporadically. The film would end with closure for Wayne, Batman and Gotham and finish off the trilogy nicely.
Until Nolan decides to make The Dark Knight Returns in 10 years time.
Obviously I've not really thought it through...