Since this question can be answered in many ways and has no single, definite answer, we will mark this question answered

I do not have any experience with this amp, but after checking out the manual, it does have a effects loop. Typically the POD's sound best when connected directly to the effects return of the amp, in essence bypassing the front end of the amp and only using the amp's built in power amp.

To do so:

connect guitar > Guitar In on POD HD500

connect Left mono output of POD HD00 > effects return of the amp

Set the POD HD500 to the stack power amp output mode as well.

If you need help understanding output modes, we have a video tutorial about POD HD500 output modes at the link below:

http://line6.com/support/docs/DOC-2562