I don't really have much of a strategy for cleaning out my drive other than just going through and looking at each file to see if I want to keep it or delete it. I might have 100 miscellaneous funny/interesting/weird movies but I realize that there are a dozen or so I don't like.
The other thing is my desktop... it gets cluttered. Not too bad though. I know someone who never moves anything from his desktop until it's completely filled all the way with miscellaneous files, then he throws them all in a "Temp" folder along with five or six other Temp folders, and starts over again. It's like waiting until every square inch of surfaces in your house/room is covered, then throwing everything into a big garbage bag and throwing it in the corner. Really, really stupid if you ask me, but I guess that's his way of doing things (he uses Windows... go figure).
So I'd say use something like Omni DiskSweeper to search for things that are taking up a lot of space, and just go through whichever folders have lots of files in them and delete a bunch that you don't want anymore. Maybe try to categorize them so you have 5-10 folders and only a few items in each folder, instead of a hundred items in a single folder.