I've used it in different ways. Currently, I always keep an mxr 10 band on flat at all times (doesn't alter the tone)....and instead of adjusting POD patches on the fly for different rooms, where you need, less bottom, more bottom, more highs, less highs...like you would adjust on a regular amp for different rooms.....I use the MXR for it. Leaving my presets in tact. There's nothing worse than soundchecking for a gig....and the sound guy goes "Hey can you pull down the low end a little...or give me some highs"...and you gotta get on the ground and go through every patch you're using and adjust the eq. HELL NO.
I've also used the effects loop with a simple patch cable jumper between the fx send and return...no pedal...and strictly use the loop for solo boosts. It's the best, cleanest way to boost for solos.
I've noticed some pedals don't play well in the POD HD loop. Some chorus's and analog delays...seem to darken things sometimes...or really alter the tone. Some pedals play nice with it though.
Another trick is...between the 1/4 out and your power amp's in or amp you're using....pedals can be places there....sort of a "line level" type of out. I have a carbon copy delay placed between the 1/4 out and my matrix power amp...and it sounds and behaves exactly like an effects loop scenario.