I'll base my experiences on what I played on the DS since it's the same thing, I've played many touch-based games and find many of them play just fine with the left hand. Including Zelda: Phantom Hourglass and Kirby Canvas Curse which were both pretty awesome.
as a lefty the only game i'm nervous about is Kid Icarus. The rest of the 3DS is fine but I really want Kid Icarus and i heard it wasn't lefty friendly with the controls. --- 3DS friend code: 0087-2310-3975 Currently playing Lego LoZ: OOT, Samurai Warriors: Chronicles, and LoZ: LA... Can't wait for Kid Icarus.
I'm left handed. I do everything except shoot a gun left handed. I haven't had any problem with the DS or 3DS. --- In order to make an apple pie from scratch, you must first create the universe. You musn't be afraid to dream a little bigger, darling.
It's pretty easy to be a lefty and play the DS/3DS games. Most games that involve extensive use of the touch screen will have options for which laterality you are of. In these cases, most menus/buttons/whatnot will be mirrored around for easier access for lefties. For the games where the stylus isn't required as much, it's simple to just hold the stylus in between two fingers of your left hand. Or you can get a screen protector and just use your fingers on the touch screen for more convenience. --- A Sig draws near! Command?
It's not as big a problem as you would think. The vast majority of games are perfectly doable as a lefty, though the ones that are lefty-unfriendly deserve to burn in the seventh layer of hell.
I've had trouble using Inchworm Animation because my left hand was moving the circle pad as I was drawing. That's the worst that's happened, though it is quite annoying. --- A horrible person: I am a horrible person. That's what it says: a horrible person.
Most current 3DS games are perfectly playable left-handed, but that's because none of them really require stylus precision in conjunction with the circle pad. However, with shooters like Kid Icarus on the horizon, I'm starting to get a little worried. --- $50 says that I don't have a gambling problem.