The first most common question arises out of an industry standard for hard drives. The industry considers 1000 bytes = 1 kilobyte, 1 million bytes = 1 megabyte, etc... When in actuality they are multiples of 1024. This article from Apple's knowledgebase explains it in more detail:
You can use the program called Whatsize to determine if there is something eating up your hard disk space:
In addition, people with older versions of MacAlly iShock drivers have been known to have increasingly large logfiles. Updating the drivers fixes this known bug.
Incomplete burns or backups with Carbon Copy Cloner will result in lost space. If you use the latter, there are instructions for clearing your /Volumes/ directory on Bombich's website.
You can typically save quite a bit of space by removing all the non-English languages from your installation (which was a customizable option when you first installed) using the utility Monolingual:
I keep my browser caches at 1 MB in their preferences. Safari does not have a manually set limitation on browser cache per se, but it can be emptied from its own Safari menu, if you suspect an issue with its own cache file corruption. Note, cache files are there to speed up access to webpages which don't change since the last visit. However, corruption can mean that the speed gained could be negligible as the browser may have trouble dealing with the files. In addition, the larger the cache, the more you have to access the hard drive, and the speed of a hard drive access itself may eventually be slower than your own connection to the internet.
If you leave your computer on overnight certain logfiles can be cleaned up and space saved. The freeware Macjanitor can force these cleanup tasks to happen:
Though I try to keep my machine cleaned up by leaving it on overnight at least once a month.
Once you have at least 2 GB free, you can burn to CD at least twice any data you may want to access at a later time but don't need immediately.
Short of these solutions, deleting files which you don't need, and backing up those which you do off the main disk is probably the best way to handle losing lots of space. Use this article as well as other good backup solutions on the net to determine what you need to backup:
If you have a question about how to simplify your backup process, there are quite a few people on Apple Discussions who can offer you some suggestions.