I had this exact problem happen twice with RX, it's created by using USB audio and then switching to the built-in out without switching the configuration first.
The first time I frigged with it because closing and opening it didn't do anything either, but the second time I paid more attention and did the following:
(with RX open and not sending audio, the usbpre2 in standalone mode)
1) re-plug the usbpre2 in usb mode.
2) Close RX
3) Restart machine (leave usbpre2 connected so it will reconnect on startup)
4) Open RX
5) switch settings in both RX and System preferences to send audio to the standard output (I can't remember if this is in the midi control or just in sound preferences)
6) Close RX
7) Pull the usbpre2 and put it in standalone mode
8.) Open RX and play something.
Essentially (in my case) there was a problem where it wouldn't flip back to another sound device until it saw the original device first and you set it manually and you can't set it to something else when the original selection is no longer valid. Yours may be a similar issue, maybe not, but it's worth a shot. Otherwise yes, I'd re-install it.
The only time I like usb audio is when I have a desktop that never gets put to sleep, otherwise I loathe it anymore.