I'm using my HD500 for two things. When we play live I use it as a virtual pedalboard between my guitar and my amp. When I record demos, I use it also as an amp modeler.
I have a hand-made Monster tube amp which is a lot like a Hiwatt but with more versatility, a very big and flat (in a good way) sound with nice distortion. I have it set semi-driven and add distortion from the HD500 (Tube Drive model) to drive it further. When I record demos, I use the Hiway 100 and/or JCM 800 model to imitate it.
In our style, all the effects work nicely before the amp, like they were pedals. I use lots of delay (Analog w/mod is my fave model) and reverb (usually Spring before the amp). Auto volume delay is very typical. Octo/Particle Verb, phaser, tremolo, whammy, ring mod, they all have their places here and there during the set.
I make patches and/or banks for each song. Usually the delay tempo and feedback are what require their own patch. For most patches, FS1 has distortion, FS3 has delay and FS4 has reverb. FS2 is dedicated to some "effect", be it phaser or extra distortion. Wah is usually accessible through Exp Toe. This way I have best of both worlds for pre-programmability and improvisation, I can always quickly add a delay if I feel like it.
I've also taken much time in adjusting the footswitches so I can go from a boosted distorted tone into clean with delay and other effects with one button, and have delays and reverbs trailing. I also often use the volume pedal or have the expression control some parameter.
I've found my favourite way to make a clean tone to put my guitar (Gibson SG) on the neck pickup and brighten it up with the Blue Comp Treb. There's just something magical about that combination.
You can hear some HD500 stuff on my band's latest album: https://consciousnessremovalproject.bandcamp.com/album/tacit It's instrumental post-rock/metal.