A question for others before I write a more thorough reply:

Wouldn't it be a good solution to move the directories elsewhere but then symlink them to their default locations? You'll need to think a bit about file permissions while doing that, but are there any other caveats?

For the asker:
UNIX-like systems such as Linux are intentionally made so that a directory can be on a different hard drive than its parent directory. So, you can have /usr/games, including almost everything on it to be on hard drive #1, but then define that /usr/games/quake should be on hard drive #2. The limitation is, you cannot have different parts of the directory tree on the same hard drive. So, if /usr/games/quake is on its own partition, you cannot have /home/plzgivehugs/artwork/bigfiles on the same partition.

...except, with symlinks you kind of can.