52 WAYS..........

39. Check settings - The default settings should be fine here. Click Execute.
Safari
You can do some of the following by resetting Safari - click Safari > Reset Safari. *Edit: Resetting Safari does not clear Favicons.
40. Clear Cache. To speed up page loading Safari saves a copy of every page in its cache however if the cache gets too large it can actually slow down page loading so its best to empty it occasionally. To do so click Safari > Empty Cache.
41. Clear History. Safari can remember every single site you have visited which can have a negative effect on its performance. You can empty it be selecting History > Clear History.
42. Clear AutoFill. AutoFill is the data is saved in forms such as your username and password on websites. As with the cache and history the AutoFill can mount up over time. To empty select Safari > Preferences then select the AutoFill tab. From here you can go through the three AutoFill sections and clear out data that you no longer want stored.
43. Clear Favicons. Favicons are the little icons you see to the left of the URL in the address bar. These can be cleared by emptying user folder/Library/Safari/Icons.
Firefox
44. If you use Firefox then you can get specially optimized versions of the browser based on your processor architecture - either G4, G5 or intel.
45. Extensions Firefox has some great extensions but they can slow down the browser so take a serious look to see weather you really need that extra toolbar!
iTunes
46. Smart Playlists These can slow down the operation of iTunes as they reload the contents of the list every time the program loads. If you have a a smart play list that does not change very often then you can either deactivate live updating (by clicking file > edit smart play list) or copy of the contents of the smart play list in to a regular play list.
Other
47. HP Printer drivers can often cause problems and use a lot of processor power so check in the activity monitor for HP Communicator, if it seems to be constantly running at 80% - 100% then try uninstalling it. I had problems on my Mac Mini for my HP PSC 1110 all in one with the HP software on OS X 10.3 maxing out the CPU after printing. I had to remove the software and just use the basic drivers rather than the full suite.

48. Check Classic is not running if not being used. Classic can be disabled from within System49. Run Software Update. The latest updates sometimes provide speed increases as well as fix bugs and vulnerabilities.
50. Update other applications. It's always best to run the latest versions of your programs. Websites such as Mac Update and Version Tracker are good places to keep your applications up to date.
51. Add More RAM. There is only so much you can do with software, the cheapest way to give you're Mac a speed boost is to upgrade the memory.
52. Reboot your Mac. After doing all this optimization it might be an idea to reboot your Mac. If your like me and use sleep mode for the majority of the time then a reboot once in a while often helps too!