From an interview with IGN about the Wii:
The dialogue turned at one point to, of all things, left-handed and right-handed gaming. Miyamoto is left-handed, and he said that he’s recently been trying to get used to using the remote/nunchuck pair in the “reverse” way — that is, the remote in the left and the nunchuck in the right hand. While he’s been getting used to playing like this, he feels lefties who’ve grown accustomed to playing games the current way will have an easier time of playing Wii games like everyone else.
In practice, regardless of game, you’ll be able to play with either device in either hand. Miyamoto actually expects kids who’ve never played a game before to hold the remote in their left hand and the nunchuck in their right hand.
So I guess that’s good news, which allays some of my fears about lefty gaming in the next generation.