Drive letter changes are handled in the background, silently without complaint. Doesn't matter to DrivePool. Change drive letters as you want, Windows Explorer acts just as before, transparently. You can even eliminate drive letters all together as I have, and just number the drives. All works the same.
I actually have one PC where my primary drive has 2 partitiions, The first, C, has Windows 7 as normal. The second partition is part of my DrivePool. I have formatted and reinstalled windows on C without touching the second partiion, or DrivePool. AFter installing DP in the new Windows install, everything was back the same as before. (You cannot install Windows on a pooled drive, must be on it's own partition/drive)
DrivePool has been rock solid for me. No issues. I am running it on a server, a NAS box, and on my main PC. If you have a need to pool drives, DrivePool will do it in the background without the need for intervention. You won't be disappointed.