That's a pain, but I think I could work around it by observing the human's use of the mouse for a while; there are some known actions (let's restrict to Windows), like clicking on start menu and some other stuff. By watching and calibrating, you could get a good idea what to do. You also might know a lot about the target environment; maybe they have totally standardized configurations including mouse speed, display size, etc.

The environment I'm thinking about is something like a SCADA control system for, say, a centrifuge cascade :)