I've used both the GT6 and GT8 in the four-cable method along with an RM4, RM100C, and even a RM20B.
My $0.02... Personally, I think the GT8 offers a lot of effects and control for the money and is extremely easy to use. However, I also thought it caused a considerable amount of tone-suck when used in front of the amp. Or, as said by the other guitar player in my band, "Where did your dynamics go?" I dunno... once I got used to plugging the guitar straight into the front of a tube amp, I have a hard time with anything that messes with my tone and/or dynamics. After about 3 weeks, I sent the GT8 back for a refund. And believe me, I really wanted to make it work, since it would have been extremely convenient to have an integrated FX box/MIDI controller with the MTS amps, but it so negatively impacted the tone/feel of the amp that I didn't even want to hold onto it as a backup unit.
That said, I also have the previously mentioned Lexicon G2/R1 pair. From an effects quality and transparency standpoint, it is significantly better than the GT8, at the tradeoff of being more expensive and harder to program. But, using a similar 4-cable method, does allow you to put some effects in front of the amp (wah, od, compressor) and some in the FX loop (delay, reverb, etc). As far as I know, the GT's and G2 are the only FX units that allow this sort of versatility. I tried it with a Digitech 2101 once (since it has an FX loop/insert between the preamp and FX section), but it sucked even more tone/feel than the Boss GT's.
YMMV, but that's my experience. Given the tone of the GT8 and the complexity of the Lexicon G2, I've decided I'm best served by a couple of pedals in front of the amp and a TC G-Major in the FX loop.
--B