Use programs like Disk Inventory X to see what exactly is living on your hard drive. Delete ones you haven't used in six months, and consider backing up your music, movies, and photos to an external hard drive to free up some space.
You will also benefit from de-fragging your computer every so often. Information gets stored on your computer in fragments, and your machine basically runs around putting all those pieces together, which means it has to work harder. Running a Disk Defragmenter will help your PCs and Macs reorganize to work smarter.