I have a DotNetNuke skin that has a single CSS file over 3,500 lines long. It contains styles for YUI, Telerik, Cluetip as well as the actual customisation of the site. The old
For firefox there is an add-in called dust-me-selectors. If you provide a sitemap, it will find all unused css styles.
If you run dust-me-selectors, remember to run it in every page of your website so you don't delete any styles that are actually used.