What can I do to speed up a Mac that is running slow? My mac seems like it is running slower and slower. While I am thinking abut installing Lion from scratch, I figure there has to be stuff I can do now to help. I have reset PR RAM recently, I have run the verify disk utility, and fixed permissions. I have seen mixed references to running a disk defragmenter. Could that help? I am on an iMac that is about 2 years old now.

I regularly run Windows XP in Parallels, Chrome, Mail.app, and iTunes.

Update: I have about 90 GB of free space. I run Onyx every month.
First, check that your processor is running full speed. Go to Preferences, Energy Saver, Options and look at the drop box down near the bottom called Processor Performance. If it is not set to "Highest", set it to that right away. This maximizes performance, but for notebooks, it may run down the battery faster. Note that not all Macs have this setting - laptops do, and my certainly my PowerMac G5 tower does, but not all Macs do.

Next, download OnyX and run the complete set of clean up and maintenance scripts and then evaluate again. Get OnyX at:

http://www.titanium.free.fr/pgs/english.html

Next, you may wish to check that you have enough free space on your hard drive. Highlight the Macintosh HD icon on your desktop, CTL-click it and select Get Info from the resulting menu. Make sure you have a reasonable amount of space left. If not, a little spring cleaning may be in order. 

There are two excellent apps for showing where all of your hard disk space has gone, Disk Inventory X and WhatSize. Get them at:

Disk Inventory X: http://www.derlien.com

WhatSize: http://www.id-design.com/software/whatsize

Both do a great job at letting you zero in on your largest disk space consumers, so that you can hunt down any rogue files (and both are freeware, which is good).

Finally, it is possible you may have some processes running that are consuming a lot of idle CPU, thus slowing down your machine overall. I had a bad widget that did this once. Open Activity Monitor and look at your "resting" CPU occupancy when you are not doing anything in particular with the machine. It should be pretty much zero (maybe 1% to 2% at most). If it not, identify the process or processes that are taking the time. What are they? Do you recognize them? Are they needed?

If you find one that is not needed, kill it and see how your machine starts to behave. If this is the cure, you will need to identify the startup item that launches it and delete it.

So, in summary then, take the following steps in order:
1/ Start with ensuring that your processor speed setting is full (applies to many Macs but not all)
2/ Then do Onyx based full maintenance
3/ Then check that you have sufficient available disk space 
4/ Finally, search for processes that are consuming an unexpected amount of CPU

Source: http://www.mac-forums.com/forums/os-x-operating-system/80467-how-do-i-get-my-mac-run-faster.html

Another place you may find helpful: 

http://lowendmac.com/eubanks/07/0312.html