You've done a perfunctory cleaning of your documents folder, deleted half of your iTunes library and parted with some seldom-used applications, but your startup volume is still mysteriously filled to the brim. Fortunately, discovering whereabouts of the lurking files responsible for eating your drive space is a task made almost weirdly simple with a utility called WhatSize.
Fire up this sub-500KB application and, after a relatively quick scan ("sizing") of the desired volume (it will scan your startup drive first, by default), you'll be presented with the following breakout:
WhatSize provides you with a hierarchical listing of all the directories and files on the selected volume, organized by descending size. This makes it extremely easy to navigate through the largest folders and look for the largest files within those folders, quickly running through the entire list and plucking items that you find useless or are willing to erase to reclaim disk space. Items are even color coded; those above 1 MB in purple, those above 1 GB in red, etc. Why isn't this functionality built into the Finder?
There's also a great "Table View" function (accessible via the Tools menu) that allows you to filter files according to size or type criteria. For instance, you can display only files larger than 1 GB, or only files (and not folders) between 1 MB and 10 MB, etc.
Here's a very brief example of how this application can save you surprisingly high amounts of disk space: Suppose you installed the iLife '06 suite, but never use nor desire the use of GarageBand. You delete GarageBand from the /Applications directory, and reclaim a measly 100 MB or so. Little do you know, however, that a nearly 2 GB directory associated with GarageBand (in fact, named GarageBand is still loitering in the /Library/Application Support folder. With WhatSize, finding this space glutton is as easy as looking among the largest directories at the root level of your startup volume (one of which will, depending on your particular filesystem, likely be /Library) then looking among the largest directories therein, and so forth. Tunneling down the file-size rabbit hole has never been so straightforward.