Me, I use both. At least I do now.

I'm a little bit ambidextrous, doing some things with my left hand, and some things with my right. Since AudioSurf only requires one hand to play, I started off using my right hand, which normally operates the mouse. Well, after about a week of playing my right hand/wrist started to get sore, so I switched to using my left hand. After just a few days practice my left hand was as good as my right, and now my left hand tends to score a bit higher.
Right hand is a bit quicker on the fastest parts of the course, but the left hand is overall more precise and seems to be able to better figure out how to efficiently snatch the blocks.
Sometimes when I play a tune for the first time each hand will have a stab at the course, battling for dominance. This amuses me. Sometimes righty wins, but lately lefty's been getting the upper hand. Switching hands also keeps my hands and arms fresher longer, something important at my advanced age.
You must train both hemispheres grasshoppa!