WickedFinger

Despite in the virtual world of the Helix god, you can do things verboten in the real world like dist pedal after an amp, but even in the Helix I just would never try to run an amp model or even a preamp into a pedal just seems like a clipping nightmare and not in a good way. I work all my presets for hours making sure I have no unwanted digital clipping on levels and make sure everything is good musical sounding gain structure. 
 
I get really good results on many cabs getting more good low end and less brittle high end by using one of my fav mics the 4038 Coles Ribbon, marvelous thing really, Varying the spacing and early reflections and it really add a more fuller sound to many amps especially cleaner ones. Since I do not use a lot of hi cuts this gives me a warmer low end focused tone you can really feel those low notes without mud. I cut ultra lows below what I produce about 50hz but hardly anything on hi cuts. Depends on every preset construction of course. But a real amp does not hard lo or hi cut, guitar speakers do not cut but slopes roll off. this is something that bugs me about the whole IR thing. You go to great lengths to model a cab and speakers but then lo and hi cut when speakers do not do that. I do not know much about the mystical magical world of creating IRs but ti seems creating some sort of slopping curve would be more realistic than hard cuts. 
 
Also the use of the Mic preamp model Studio Tube Preamp with the impedance on line 10.0 and gain at 4.0 which is clean but imparts a subtle "tubeishness" to the sound in front of about any amp. 
Overdrive is a tricky beast I try not to get too much gain from a pedal and more interaction to the amp model gain. As far as the full on distortions on the Helix I do not really use them. I loop out to my fav drives and a high gain (Mesa Tone Burst, Mesa Flux Drive and Palladium Gainstage for cleaner amps). I find the on board fuzz and what not pretty brutal, got some good tones out of the Rat model but have not spent the time to really EQ and work on them. Probably need something after them to harsh it down a little.