"You WILL seriously mess up an SSD or a Mac hdd by trying to Defrag them"
Seldom on MacRumors have I seen a posting as ridiculous and uninformed as this one is.
Defragging DOES NOT "mess up" a drive with the Mac OS, and in some instances, is necessary to keep things running smoothly (specific examples: where large amounts of audio or video data are recorded, it's necessary to defrag so that large contiguous areas of the drive remain free to accept such data in continuous streams).
To the original poster:
I'm going to _guess_ that the reason that Drive Genius can't unmount the drive to defrag it, is because you have SOMEthing "open" or being accessed on the "target drive". So long as this remains open, the drive can't be dismounted, and you can't begin the defrag process.
Here's how I would try to do it (may or may not work):
1. Boot from the drive that DOES NOT have to be defragged, then
2. When you get to the finder, "manually dismount" the "target drive" by dragging its icon to the trash.
3. Now launch Drive Genius and go to the defragging panel
4. Does the dismounted target drive appear there? (again, it may or may not, depending on how Drive Genius "views" drives that are dismounted but still available "on the bus", so to speak)
5. If it DOES show up (even though it's not mounted), try defragging then.
I believe some other previous posters mentioned that defragging may not be advisable for solid-state drives. I've yet to own one, so I can't comment on that other to say that it might indeed be true (at least for _some_ SSD's), probably due to the way their controllers work. In that case, the best way to "defrag" the contents of an SSD would be to "dupe it" to another volume or partition, re-initialize it, and then "copy the contents back" with a "re-dupe". The files will be copied over contiguously, and the drive will then be effectively defragged.
I have defragged flash drives numerous times without problems.