I have a 20 iMac and an AppleTV 2 (the black one), and three external drives (2TB, 1.5TB and 1TB) that house all my music, movies and tv shows. Up until now, I've never needed more than the one drive for everything, but now my 1.5TB drive is almost full and what I'm doing to keep things organized feels like a cludge so I'll just explain what I'm doing and hopefully someone will tell me what I'm doing wrong and how to fix it. Right now, I'm using the 1.5TB (music, apps and tv shows) and 2TB (movies) for my media. After I've converted, tagged, etc. all my new shows or movies, I change the preferences in iTunes to the drive that contains whatever I'm about to add to the library. For example, if I'm going to add a new movie, I switch the "iTunes Media Folder Location" to the 2TB drive, add the movie, then change the preference back to the 1.5TB drive. This just seems silly to me, and I know I could create a RAID but I don't want to move all that data around so there has to be a better way to do this.
What I would do is:
This way all your data will be organized by iTunes except for the large files that should belong on your largest external disk in the first place.
I'm not sure this actually works, but it should. The only solution I can think of is to replace the Movies/Music folders in your "main" iTunes folder with alias folders (or symbolic links) to the corresponding folders on separate hard drives.
You would need to ensure the hard drives were always mounted when using iTunes.
That said, I think the best solution is to get an easily expandable external raid or NAS enclosure like the Drobo or ReadyNAS.