If you mean getting rid of unnecessary programs or files, yo can do it manually, but there are some apps that do it for you in a more consistent way, for example eliminating unused languages from other applications, etc. You can save a few Gb with this programs. I personally use Drive Genius, but there are free apps out there.
Regarding defragmentation, it's a common myth that Mac hard drives don't need it, and I agree that under normal circumstances it's true. The same is also true in Windows Vista or 7 (have a PC for over 2 years and I haven't needed to defrag it yet). Only when you work with large files and your HDD is reasonably full, you start running into problems. In my case, I have an Early 2008 MBP with 200 Gb HDD that was a little over 60% full. Fragmentation reached around 30 % and I noticed because the computer was getting slower than normal, so I got Drive Genius. After getting rid of a few Gb of unused files and defragmenting the unit, everything came back to normal.
The problem is that there are no free Defrag utilities for Mac that I know of, while Windows has a built-in utility.