I have a massive library of digital photos going way back. Add the movies, music, etc. and my media library is immense, so that's one external drive.
The other is a Time Machine backup disk. I keep them separate so I have a backup of my media drive on the TM backup in addition to the OS disk in the Mac.
The third use is an iTunes sync cable. I still sync and backup my iDevices on a cable, probably the only person who does.
Fourth, until I stopped shooting Nikon DSLRs a little while back, I needed a card reader because no laptop has a CF card reader. The rMBP has an SD card reader, but the rMB doesn't, so that's a fourth use for a USB A (or, someday when I've replaced all my externals, a USB C) connection.
Mice and external keyboards (when used) are strictly BlueTooth for me.
About a month ago I experimented connecting the two drives to my rMBP via a powered USB 3 hub. It worked great - for a while. Then, for some reason I couldn't figure out, the TM disk got sightly out of phase with the media drive and the OS drive. I got it straightened out, but haven't figured out why, and having a TM disk messed up is a really unappealing idea.