I haven't really gotten great results stacking distortions, but using combinations of distortion x/y and filter blocks for gain boosting works great.
I run my amp settings with the drive down (Hiwatt, Triptik, and Corncob are my usuals) and master volume up. I dial it in so that I can get some grit if I really dig in, but it's generally pretty clean. I also keep a very clean model on the "Y" side of the amp block for super clean stuff with no grit.
I then run a filter block for a boost right in front of the amp, I dial the amount of gain to get a nice crunch, but not something that's going to give a ton of feedback and sustain. It's more a good classic rock sound but not so great for palm muting and leads.
I don't really play metal, but I do need another notch where I can get some more balls. So, in front of the filter, I put a Rat or TS808 distortion. I set it so that with the filter and drive engaged I get a really good high gain crunch. I generally get my distortion from the output level of the drive block, as opposed to cranking the drive setting. This way I basically have a transparent boost in the filter block, and a very slightly colored distortion from the drive block. But in both cases, I'm pretty much using the amp's distortion.
On the "Y" side of the drive block, I have a Tube Driver with the drive pretty high and the highs cut, so I can get a really thick, sustainey lead tone. It's a little dark for rhythm, but sounds great for solos with a ton of delay. I have another filter block after everything for a pure volume boost for solos.
With this setup, I can do the following in one preset:
Scene 1: Heavy rhythm (Amp X + drive block + filter boost)
Scene 2: Dirty rhythm (Amp X + filter boost)
Scene 3: Sorta clean (Amp X only)
Scene 4: Super clean (Amp Y only)
Scene 5: Leads (Amp X + alternate drive block + filter boost)
Every one of these scenes has a slightly different flavor of distortion. I pretty much play an entire gig on one preset, unless I need a different setting on a harmonizer or a specific effect for a cover song. Dave Gilmour did something similar, running a Big Muff into a Colorsound boost into his Hiwatts.