I am left-handed, William, and find the Reader just fine to use. Holding it in my left hand, by thumb falls naturally on the page buttons on the left side of the screen.
I'm not sure it's true to say that Sony necessarily have to accommodate Mac users. Microsoft never have done with the Pocket PC, and nobody could say that it's been a failure as a result. Obviously, though, it would be good if Sony were to do so, but would you consider it a priority compared to, say, adding features like searching?