First rule of amp sims is put the maximum amount of effort in to finding a cab IR that sounds good! That means, select your amp sim, adjust the gain to get the desired amount of distortion/gain, leave all the EQ knobs at default position, then go hunting for an IR that sounds close to what you want. That is the greatest effort to reward pay off to getting a good sound.
Then, and only then, do you start applying the tips below. I'm not a pro, but I'd like to think I have experience that is relevant. If you have a good amp - IR sound right off the bat, then taking it from a good sound to a great sound is much, much easier.
Do a search around here and look for the Andy Sneap multiband compressor preset.
If you can't find it, I'll post a screen shot of the ReaXcomp settings I use.
Also, using an eq, set up a band pass at 1 octave and 3-6 dB boost and search around the 500 - 800 Hz range, until you find what Ermz calls the "cardboard" zone. Once you find the frequency (source dependent), reduce the band by -3 dB (or to taste).
Then do the same thing in the 200 Hz range.
Then, if you're panning hard left/right, use a Mid/Side mixer (there's a JS plugin for that) to reduce the Mid split, that will also tend to reduce the boominess of two L-R panned guitars.
See how you go with that and let me know if it helps!