An obvious solution would be to separate the wheel from the button. Put the wheel more towards the heel of the mouse (away from the cord) or at the tip. Chances are that if you're using the wheel, you're probably not moving the mouse a lot at the same time, so making it slightly harder to reach doesn't seem to be a big deal.

Of course, people make mice for Windows users, where the middle button goes virtually unused. In Unix (or X, really) I use it constantly. It pastes the currently highlighted selection -- swipe with button 1, paste it with button 3.