I wanted to do this too and have found a good sound. Although  I use the 4 cable method or 4CM with an amp, you can probably just use the od's, distortions, compressors before the Pod, then in your amp patch insert an effects loop and put your mod type boxes in the loop, then run out from that to your mixer.  put the effect loop patch just before the amp sim. then try after to what sounds better

I use the above method but with 4CM and the pedals all sound great.  be sure to set your levels proper in the mixer as to not overdrive your mixer channel which would sund like crap unless it's a fine old tube mixer or something

If that does not sound so good then try running it without the loop patch.  I've also had some luck running everything straight into the mixer.

I'm sure there is a more technically appropriate way to do it and that someone will pipe up to say so, but in the mean time I'd give this a shot.  seems to be the most straight forward method.  be sure to set your output in the POD to direct or studio
yo

I use several different pedals in my setup and they sound fantastic with the POD. I have a Hotcake Overdrive, Eric Johnson Fuzz Face, Vox Satchurator, BBE Boosta and a Deja Uni-Vibe in conjunction with the POD.

In the past few months ( I admit I struggled to get the tones I had hoped for initially) I have had many people comment on my tone and say how awesome it sounds. Always a good thing. Didn't always get that with my last setup!

I've only used overdrive/distortion pedals in front of it but they've worked pretty well.

The Boss Metalzone sounds exactly like the one built in the HD500 I have, but with a few more tone tweaking options. Other than that though, spot on.

So if you have pedals you want to use with the HD500 go for it.