In order to get the better results in order to use the POD HD500/X with the 4CM I recommend to use these settings:
1) Turn to maximum the volume level of the POD, I use an additional expression pedal connected to the POD to control the volume
2) put the switch of 1/4 output to AMP mode
3)put the FX switch on STOMP mode
4) Insert the FX block (send and return after the mixer), set the send level to 0, the return level depends by your amp, in my classic 30 I have to set him around the +12dB in my laney Ironheart on +6 dB, try to find the one that better fit your amp..
5) In the mixer put the pan on 0 for both path and the level on 0 dB for Both path...
These settings works pretty good....
Personally I use the amp sound so I put som effects before the amp (wha, noise gate, compressors distorsions, tremolo phaser, flanger etc..)and others after(equalizer (to boost for solos), delay reverbs chorus harmonizer , and volume pedal at the end).....
occasionally I use some preamps models...In my opinion Soldano Crunch,Pete amp, Mahadiva, Brit 800, Plexi lead normal work pretty good..
In these cases I put the output model on Combo power amp, and I use also the cab models of preamps...
For global setting in my pod HD500x I set Guitar for both guitar inputs and in general I use the 3.5MHom as input impedence level...In my opinion in this way all the dynamic of my guitars is preserved....
I hope this can help the Line 6 community.
Regards