Here is one way to do it.
I use a Ground Control Pedal board and a Digital Music Corp GCX to split the signal into two separate signals (Any ABY pedal would do it pretty much just as well if you don't need to change guitar sounds radically)
The signal is split between a Fender Prosonic (2 channel amp) and a Pod Pro XT.
The Pod Pro XT is set up to have two basic sounds that are similar to the Prosonic (I use the Matchless DC30 emulation for clean and the Engl Powerball model for crunchy).
If I am using delay I set the Pod Pro to be 100% wet so that you are only hearing the delayed sound with all the other effects tailing behind it.
I have volume pedals for both rigs- so I can switch between 100% Prosonic or 100% Pod- the POD also have a whole bunch of looping devices added to it that splits the signal a couple of times so I end up with a bunch of independent loops.
The ground control is controlling everything so switching channels on the amp occurs at the same time as the patch change on the POD.
This way you get the sound of a tube amp dialed to 10 (or in my case, 6) with the wet effects added and no loss of tone.
I use a Gallien Krueger 800RB amp for the wet guitar tones to a 4x12.
If you're interested in how it sounds have a listen: http://www.lotusthrone.com/Scape1.mp3