The Diablo III Game Director Interview on G4tv.com chats with Jay "Shade" Wilson about Diablo III, Blizzard's upcoming action/RPG sequel. One point of interest they highlight separately is about how they will try and make the endgame interesting even after repeated runs:

It’s definitely better if the players explore more of the game. It will be a lot more fun for them, but players will gravitate toward the route that is fastest for what they want. Even if that route makes them crazy… even if that route is not fun at all. It’s not their fault. It’s our fault as designers. It’s our job to make sure that the path of least resistance is also the path of most fun.

We do have specific systems planned for the late game and our goal for those systems is to make sure that players are experiencing as much of the content over again as possible.