I've played all the games in the main series (except Skyward Sword, obviously), so I'll have to go with a spin-off. Obviously, from what I've heard about the story, I think it might be interesting to play Freshly-Picked Tingle's Rosy Rupeeland. I'd have to play it on my old fat DS, though, since I'd have to import the PAL version and the 3DS is region-locked.
If replaying games with different conditions counts, though, I'd like to try and play through Link's Awakening DX on 3DS Virtual Console (which I have yet to buy) without ever dying. This would of course require some resetting manipulation, but I'm up for it, and I'd like to earn the special ending. I'll go ahead and mention that I'm SUPER excited to play Skyward Sword once it comes out.