I have been running my original version of NWN from my portable drive (USB) for the last year, it is prior to Diamond edition but with the patching all worked well, it interfaces with vista fine (had only a couple load issue on the first run but this sorted itself out) as this is what runs on our home computer, at work it is old windows version and never had a problem.
Found this the best way to run without having to continually reload it onto different computers, as I updated or moved.
I tested the diamond version too on a separate drive and this worked well too.
The program is not heavy enough to cause any slow down using a portable (USB2) drive.
Clar