I think it does need to be radically different. Twilight Princess should be the last game they make in the vein of OoT. I would like to as many as possible of the following added in the next iteration:
Steam Punk or Darker Medieval Artstyle or go the other direction and make it a painting or Cell Shaded like Okami/Wind Waker
Voice Acting for everyone but Link
Orchestral Music
Wii Motion +
Larger World on the Scale of Everquest or WoW
Ability to actually go into every building and have a more living world like Oblivion but I don't want a Western RPG... It should still be scripted...
Much more complex story (Waring Nations/Intrigue, Romance, etc.)
No More Ganon (He's played out)
No More retarded Mail Man or Tingle
They don't need to make a game with a gimick (ie flooded world, light/dark world etc.) for it to be a good game, just make it have an epic story and great gameplay and that is all I need.
If Nintendo can't do this, they need to give it to someone who can, because despite me still loving Zelda games like Okami and the Team Ico games a so impressive that they are making Zelda lose its lustre in my eyes.. This is all IMO of course...