I run my amp through the clean channel totally dry with some good tube warmth but no hair or distortion. I run the guitar straight in to the 11R to the input of the amp. Simple as that. I tend to keep the break-up on the speakers low in my simulations, as I get speaker break up from the actual amp/cab. Singtall sounds are always a good start with this system.
This works with my Carvin Legacy, Black label Krank, Crate VooDoos, Marshall and even my Little Stiff. My guess is the Krank is as close as I have to your Mesa. The effects loop never worked worth a crap with the Krank and the 11R. Plugged straight in to the input and I was done!
If you are close to me, come on over and we will work it out.