@ryancwynar You wont need to change layouts when you switch hands because your memory map of the layout will be the same as the orientation of the keys have not changed. Its like typing on a regular keyboard with just your left hand then moving to just your right hand.
The only thing you would have to change is the location of the strap.
If you would like to have two different configs just name them twiddler_left.cfg and twiddler_right.cfg and store them on the Twiddler. Copy the appropriate config file over twiddler.cfg and it will instantly start using the new config. In fact, you could probably store all the commands in a chord so that it would automate the procedure.
Twiddler mounted on T:
<Left GUI>R</Left GUI>copy /Y t:\twiddler_left.cfg t:\twiddler.cfg <return>
<Left GUI>R</Left GUI>copy /Y t:\twiddler_right.cfg t:\twiddler.cfg <return>