In the game, Mickey has to save a world full of forgotten or rejected characters from throughout Disney's history. Both the Phantom Blot and his long-lost half-brother Oswald (yes: Oswald the Lucky Rabbit!) are key characters.
I think this is may be one of the best games this year. Spector (the creator of System Shock and Deus Ex) was given a high degree of creative freedom by Disney, as well as access to their extensive archives. Spector has been mining that history to create a game environment right in Disney lore.
Since the entire gameplay is based around Mickey "painting" with his magic paintbrush, Epic Mickey will be Wii exclusive.
Check out the opening movie on YouTube.
Gamespot also posted a lengthy interview/walkthrough with Spector from E3, and it contains a lot of gameplay footage.