On gain, I have seen lots of people say that high preamp gain worsens the sound in some way, but if you set high preamp gain and add a gain plugin before the amp modeler to bring the level down and compare it to lower preamp gain at the same total level going into the amp sim, it should sound pretty well the same.
It’s really about how much gain the amp modeler is expecting to see at it’s input, the same as with an amp. This is assuming that you are using a hi-z input for full fidelity of the signal and not clipping the input converter, of course. Problem there is plugin developers not providing any info on what signal level their amp modelers are expecting to receive for an accurate correlation of what the real amp equivalent wants to see at it’s input. Amplitube and Tonex catch a lot of flack for this, and rightly so. But it’s ultimately up to what you want to hear, just the same as with real amps and choosing pickups with less output or more output, using a clean boost, a treble boost, or boosting with an overdrive. Hit the input harder, and you get more gain, because the power supply in the amp (or model) runs out of steam to cleanly produce the input signal. But pushing the input might make mud due to presence of lower frequencies in the guitar signal getting distorted, which is why the treble booster pedal was invented, to put the push in upper frequencies and avoid the muddiness of distorting lows. And this is the same principle of using an overdrive as a boost, where overdrive pedals typically have a humped mid shape with less lows and/or highs to keep things ‘tight’.
Personally, I often like a little mud in the bottom, which I used to not like at all. Depending on the amp, it can add a lot of character. Fender tweeds, JTM45, etc.
That said, the reason that higher input gain can make an amp modeler sound worse is that the full frequency response is getting the distortion treatment. But it’s not really at all about whether the push comes from the preamp of the interface or from a gain plugin. If you want a pushed sound, try using an eq plugin as a booster before the amp modeler to roll off or shelf down some lows, hump the mids, etc. You might be surprised at how effective it is, and it’s way more versatile than any overdrive pedal can be.
And talking about mud in amp sims is directly relative to what goes on inside guitar amps. After Fender tweeds, more internal filtering began happening to tame the bass from getting distorted (same principle as a treble booster or overdrive), i.e, there are little bass frequency filters at each preamp stage along the way. Over the years, guitar players wanted more gain, and so more filtering was added, eventually arriving at modern Djent sounds. All that pushing, clipping, and filtering also removes purity of the guitar signal and reduces dynamics and touch response, where with simpler constructed amps there is more interaction between the guitar pickups, the amp, and the speakers, because the tiny guitar signal is more directly controlling the big ass DC power supply current that is pushing the speakers.
Check these muddy suckers out.
JTM45’s were copies of Bassman’s, using parts that the Brits could get on their side of the pond. Both getting real loose, which is the bass end being distorted. Personally I think that looseness (mudiness) has a lot of character.