When I plug my Pod X3 Live into the guitar input of my Marshall tube amp, I get drastically worse sound than if I go through FX loop. I have changed the switch for "amp" output instead of "line" output, and I have set the "Outputs" setting to "Stack Front" instead of "Stack Poweramp". Any distorted tone is super fizzy and terrible, but if I go through the FX loop, even with 100% signal coming from the Pod for the wet/dry mix, every tone sounds just gorgeous and dead-on what I expect. I've made sure the gain isn't cranked on my clean channel on the Marshall, and I can't think of what else would cause this... any ideas?
The reason it sounds better in the effects loop is because you're not running it directly into an overdriven/distorted signal like you would be if you were running it into the front of the amp. The two signals are separated.
I see - so really, when running through the front of anyone's tube amp, it sounds like I'd be better off bypassing any amp modelling and only using it as a multi-effects device. When recording or running through an FX loop anymore, I should be able to get the best of both worlds... right?
A good rule for using effects is this;

Modulation effects should always go in the FX loop (Phase, flange, delay, chorus, etc.)

Regular effects should go into the front of the amp (Overdrive, distortion, wah, etc.)

So yeah, you should be able to get everything you're looking for when you have your amp set up like this ^^

Hope I could help.