IF they are U3 drives, the U3 people have always stated you NEED to use their un-install program to remove the auto-mounting of the emulated CD-ROM drive. (Don't know for sure as I never removed any of mine.)
Rick Glazier From: "Ben Ruset"
If there's stuff on the drive that you don't want or need, then by all means format it. It shouldn't be required to use the drive as a basic USB disk.