I noticed recently that my hard drive had shrunk by several, if not a dozen GB. The phenomenon shortly followed a smooth upgrade to OSX Lion who became suspect #1 shortly. And in vain.
Then I turned towards the other usual suspects, namely caches. For these, a simple restart does most of the cleanup and reclaims several GB if your machine has been up and running for a long while (several days if not weeks).
Focus really came to iPhoto when I realized that some changes made to pictures within iPhoto did not reflect on my iPad2: pics were preserved, but did not show up in their latest version.
So I opened the iPhoto packet (Ctrl-click) in my Images folder, sorted content by size, and found that the iPod Photo Cache was 19.6 GB = 25% of my total iPhoto library size...
This folder holds all the resized versions of pictures you sync with your various iDevices: in my case, many of the iPhones I had used in my former business lives along with two iPads and a now old iPod Photo... Even if it sits in the iPhoto packet, the iPod Photo Cache content is actually manipulated by iTunes at each synchronization session.
So I quit iPhoto, trashed the folder, and went for 2 long sync sessions (iPhone and iPad) as the whole cache had to be regenerated. Now my pics are in sync again, and the new cache folder is 85% smaller.
Tell me about yours.