Are you using straight extraction or GOD installs? If the latter I would not worry about it (GOD installs are effectively just a bunch of larger files) as it will do little.
If doing extraction I still wonder about how effective it might be but I am not sure as I do not know how the disc read API functions and the more generalised things play off each other and how this translates to defrag programs. This being said you can always go the other way and move everything off the drive (so as to end up with a bunch of free space) and then move it back- most things should be written sequentially upon return of the data and thus you have a defragged drive (all defrag programs do is take data and shuffle around the drive (possibly with a stop over in memory) to make it all line up).
Not to mention even a slow hard drive is far slower than the DVD drive (they stopped at 12x I believe- thinking some of the older hacked DVD firmwares that let you pick slower speeds) which translates as about 16 megabytes a second or about half of a USB drive (let us not start a debate as to seek time, protocol overhead and whatnot) and probably even more for a sata drive.
Also "lot of stuff"- if you have just deleted things as they returned or just added files to the thing without deleting and adding new files then chances are it is not even that fragmented.
Indeed these days unless I am lumped with an older 5400 rpm drive or trying to improve some database driven program or do the PC game bit I do not even bother defragging machines when cleaning them up (even then it is file specific and maybe a spin on the windows/program files directories).