I’d been getting the spinning beachball entirely too frequently using Safari lately; I even tried switching to Firefox, but didn’t feel like migrating all my bookmarks and such, so I went back to Safari.
I was pleased to find a tip on macosxhints to help speed up Safari. It turns out my major headache was the “other forms” autofill cache (mentioned by a user towards the bottom of the discussion thread), but I also took the opportunity to clear out my favicon cache, the nominal goal of the hint.
You should try Cocktail (http://www.macosxcocktail.com/). It cleans out your local and user caches, prebinds, runs maintenance crontabs and everything else you can think of to give OS X refresh. You can even schedule it to run unattended. Well worth the ten bucks.