It's obviously going to dramatically effect the marketing. The actors still involved will be unable to talk about anything other than Ledger. It will be impossible for subsequent trailers and TV spots either to ignore him or to focus on the evil of his role.
It has the potential either to completely derail the movie, or to make it one of the most memorable classics of all time.
As for the future of the franchise, well, I suppose it reduces the chances of The Joker being seen again. It may even effect the way that TDK is cut, perhaps to avoid a death scene or anything too harrowing involving Heath. I can't see how another actor can step into his shoes, now. I would imagine that it reduces the chances of the existing cast and crew making a return, as well.