5/5Diablo III is a great game for people with disabilities, as long as you can move the mouse effectively. Given that moving, attacking, speaking to NPC's and picking things up are all done with the left mouse button, you could play pretty effectively with just a single input, such as a switch. However, it's handy to have the secondary ability and the action bar bound to the foot pedals too.
It has a nice flexible key binding system too, so that you don't even have to set up a layer in X-Mouse Button Control, just bind the keys in-game.
Disclaimer: I have only played a Wizard, other classes may be less playable.
Mouse Bindingsleft button - Same as default profile
right button - Same as default profile
middle button - Same as default profile
In-Game Key Bindingsmove / primary skill / interact - left button
secondary skill - right button
action bar skill 1 - MBWHEELDOWN