A lot of people seem to be saying that using the preamp sims with a combo preamp doesn't work.... that you should either forget the preamp sims or bypass your real preamp.
But my advice to anyone in my situation (combo amp, no effects loop) is just experiment and you might get a good sound. I run the GT6 into the main input on a Marshall/Park combo, I leave the combo on a clean channel, and use the GT6 preamp sims - especially the JC-120.
It took me a long time to balance the different level controls (patch levels, gt6 main output level, amp level) but now it sounds great. Adding my combo's preamp after the GT6 (rather than going direct to PA) seems to make the sound more touch responsive - so the message is you can get anything to work if you tweak it enough!
Anyone else using a similar setup with success?