Is it safe to delete ~/Library/Caches/com.apple.iLifeSlideshow/Pictures?

Solution 1:

By design intent, files stored in ~/Library/Caches should always be safe to delete, at least as long as the application isn't running. You can mitigate any poor programming bugs by moving them to trash and then rebooting the mac before you empty the trash as this ensures whatever programs are running can still write files to that old cache directory but will be forced to make a new Cache folder the next time it starts.

In your specific instance, the folder/files in question are created by iPhoto when you start a slide show. It seems that they do not get removed when you exit iPhoto later on so you have to remove them manually if you want to recover the disk space.