I’m facing the same problem, i’m trying to use the QC as an effect directly to the my Mesa Mark V Amp and my guitars sounds dull and all the harmonics are gone.
I’m connecting it without any effect on the chain, i also tried the 4 cable method and with very short high quality cables(mogami) and it’s very disappointing to find-out that it’s removing all the harmonics and the brightness of my guitars.
Can someone from Neural can help us?
I’m the OP for this thread. I learned a lot by using someone’s suggestion to start troubleshooting by deleting all blocks from a preset and checking the sound, then adding stuff one at a time to see where the top end starts to roll off.
Using that method I’ve also discovered that the factory amp models tend to distort even on clean amp settings (unless you set the input gain for the QC way low). I’d call that a bug or maybe a design flaw. And that may be contributing to the top end issue we’ve encountered, so check it out.
Since I’ve been more detail oriented (a la the above) in my troubleshooting, I’ve been much happier with the sound. “Just don’t use blocks or settings that suck” seems to be the answer. 
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LOL! Every modeler tutorial should begin with this. 
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How low do you mean? Like what is your gain setting at your input?
I look at it a little differently. When performing, I have the volume knob only controlling my onstage monitor, not FOH. That way I can quickly adjust the volume of my monitor from the QC without impacting FOH. Additionally, I am sending FOH a consistent leveled signal with an optimal S/N ratio. I run the volume knob as high as I can but leaving some room on the dial for up or down adjustments.
If it’s a design flaw, it’s one I have encountered on pretty much every modeler I have used. Usually, the solution is to keep the master volume higher and the gain low if you are looking for clean sounds on the amp blocks. Just like a real amp. Cranking up the mids or bass too high can also create a “dirtier” sound. I do agree that there are amp models (on every modeler I have used) where it seemed like they should have cleaned up more without having to resort to such low gain settings.
Sometimes you select an amp block that just won’t clean up well. Best option is just to move on to one that does. I try to find an optimal input level that works with all my presets. It all goes back to proper gain staging. As you mention not overdriving everything downstream is important, but I don’t want to have to lower my input setting to a point where I kill my S/N ratio and actually introduce additional noise. Entirely counter-productive to getting a clean tone.
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@747 I set my input gain as one would expect, which is to say so that it peaks on my hardest strums just into the red. Like this guy shows: https://youtu.be/eKSYHPMCTLk?t=51
Then I avoid any amp models (or any models, ideally) that do what I don’t want—like distort at their input when receiving signals at this nominal level. If I just have to use a particular model that has this problem, I’d be sure it gets a low enough signal level to preclude this misbehavior.
I haven’t had to do that yet, but my first thought would be to put a pad of some kind in front of it for the current preset, rather than reduce the QC’s input level, which would, of course, impact all presets.
UPDATE: I see I haven’t actually answered the question as you intended it (I think). In order to get any of the offending amp models to present a truly clean sound, I would just reduce my QC input level until that goal was achieved. I don’t recall what that setting was. My guess is it would be different for each offending amp model, though I could be wrong. I do know that it was much lower than I was happy with. Like below -10 or -15 (as shown on the virtual input knob’s indicator). With the signal peaking WAY below the typically-targeted red zone on the meter.
@HonestOpinion I would only add that the distortion I hear (with the input gain for the amp block turned all the way down) doesn’t even sound like a “good” clipping, like I would expect from an amp. It sounds like something else. I’d call it unwanted hardware distortion, but since it appears to be an artifact of the block itself (software), that can’t be right.
I prefer not compromising my QC input setting to appease problematic models and so would instead reduce the level going into said model with a signal-reducing block preceding it. That said, I haven’t tried it yet. But I assume it would work.
That may be the problem. Try to set your input to 0 and then look/listen how the amps behave. That’s how modellers and plugins seem to be designed. Which may be counterintuitive coming from the analog world, but makes sense in the digital world.
Or think about it like that: when you go from your guitar straight into a real amp, you don’t boost the guitar signal. So why would you on the QC?
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@747 I think we may be misunderstanding each other. What I’m expecting doesn’t involve a boost of any kind. It’d attempting to achieve the unity gain that the amp would be expecting from the guitar.
I’m talking about the offending amp models requiring the QC’s hardware input level to be set way below nominal, as indicated by the input peak meter. Otherwise, what’s the purpose of the nominal point (bottom of the red zone) on the input peak meter? I see that as a away to set up unity gain into whatever block (including amp models) show up in the grid. As such, an amp model block should be expecting that unity gain to be the same as plugging a guitar into the amp it’s trying to emulate. Would that not be the way this stuff is intended to work? And if not, again, what is the point of the way the input meter is calibrated?
But you are boosting the signal. Because that’s what turning up the gain on the input of the QC does. Just try it out at 0.
Or is it turning it down?
It’s all relative. That’s why we have a reference called unity gain. That’s what the nominal point on the input meter is for. Right? Otherwise, I say again, what is the point of the input meter?
How can one know what level the amp is expecting at the input? The answer would be (it seems to me) that they are all looking for what the QT has established as the nominal input level. As defined by the calibration of the input meter. No?
BTW, setting it to zero isn’t enough. It’s got to be WAY lower.
It’s not relative. +0dB gain at the input is unity gain. Turning the gain up means you are boosting the signal. Turning it down means you are lowering it.
The input meter simply shows you your signal strength, which you can adjust depending on your instrument. But you don’t have to.
Again, in the real world, if your guitar goes straight into the amp you adjust the gain on the amp itself. With the QC you can do the same thing by leaving the input at 0dB and adjust the gain on the amp block on the grid.
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Okay. Let’s call that unity gain. The problem is that when I do that, I get the distortion I’m talking about. That’s why I have to turn the QC input way down. This is why I’m saying the amp models are bad. They don’t act like the real amp. They distort when I replicate the act of just plugging in my guitar. This is the problem many of us are having. I bet you will have the problem as well if you do a test.
Set your QC’s input (virtual) knob to zero. I use input one, on a quarter-inch TS plug, which may or may not matter. Clear the grid and place a single Fender Twin factory model amp block (not a capture) along with a speaker cabinet block after it. Set the amp’s gain knob to one or two. Hit an open G or open E or a barre chord hard. If your unit acts like our units, you will hear unwanted distortion.
im gonna guess either your guitar or the QC need repair. Most likely an issue with your guitar though
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Guitar problem? 
I turn the QC input down and it stops distorting. How could that be a guitar problem?
Having worked with lots of bands on tons of albums it’s wild how many of their guitars have weird issues with the electronics that haven’t ever been noticed in a practice space through a loud amp.
Seems very strange that you have to turn the input all the way down. Might want to get your QC repaired because its theres no way it should need that
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I also configure my QC XLR I/O for unity (0.0dB) gain and haven’t had any issues. Do you by chance have Global EQ enabled? Didn’t see that mentioned anywhere and often catches some off guard. Has support recommended to backup, reset and restore? What else have they recommended as of current?
Sounds clean to me. Can you make a screenshot / picture of the input signal on your QC while strumming reasonably hard?