The best tip here was to put your filter block behind the FX Loop on the layout. That made a huge difference. I've been doing a ton of experimenting with my AXE FX and my Blues Deluxe tube amp. After going at it for almost a year I still go back to the responsiveness and complexity of tone a real fender amp gives me versus the AXE through my QSC K12 and my AXE FX through my BWG power amp and 2x12 JBL D120 Cab. My Blues Deluxe also has a JBL D120, so its a great speaker and can function like a FR Monitor in terms of reproducing sound versus colouring it.
What surprised me was that I'm gravitating towards using the amp and cab sims in front of the BD's preamp. Sure they colour the sound, but they also act as mild clean boosts with a touch sensitivity to OD when I crank up my guitar volume.
So far I'm using the 4CM. But I also have a Silverface Vibrolux. Can anyone shed some light on the never really mentioned old school one cable method. My results on the 4CM is its a tone sucker big time when I'm trying to let the Blues Deluxe just be itself, and the one cable method is giving me more grief in terms of amplifying noise.
For the sceptics out there here's a demo I put together comparing the various setup options - 4CM, Amp as a poer amp only and straight digital.