I'm a lefty, and love my 10/22. Power Custom makes a big-head safety that can be installed for lefties, but that's the only hand-specific mod that I can think of.
Browning used to make a .22 semi that fed from a magazine tube in the buttstock and ejected from the bottom of the receiver. Don't know if they still make it, but it was pretty pricey.
Savage makes some of their bolt-action .22s in left-hand versions, as well.