FWIW, I do this quite often with my Aguilar TH500. I'll run an external preamp (either a tube preamp, or my pedalboard, or whatever) into the FX Return, which bypasses the whole front end of the amp and goes straight into the poweramp. It's a great way to make the most of the equipment you have available, rather than having to buy different amps for every flavour of the week. Plus, if anything ever happens on a gig , you can just unplug the preamp and plug into the regular Input on your amp as an instant backup.
One thing you can't do with this method, however, is easily switch between your external preamp and the amp preamp. Once you're plugged in to the FX Return, you'd have to unplug that and plug in to the front if you want to switch. So this method doesn't really work as a "Second Channel" effect or anything like that. It's all or nothing.