I have my laptop set to never sleep as I also use it for some home automation stuff... I also use InsomniaT to prevent sleep even when the cover is closed), so USB shouldn't be an issue.
as long as the usb cable never gets disconnected and nothing causes the system to not see it, then you're correct in that it won't matter.
Pissed me right off the first time it happened to me, had to save all my stuff, shut down RX and reconnect everything proper. I screwed up twice like that and quit using the usb interface afterward. It works for some, but it's not for everyone. Best of luck.
edit: btw, if you're using usb audio in osx, make sure you're at
10.6 or newer. There was a bug in full duplex mode that prevented the system from using it regardless of whether the hardware supported it. SoundDevices and I dickered around with that (and some other bugs) for a while with my usbpre2 and thats when I discovered it.