I'm using a Hot Rod deluxe (1998 Model) and a POD HD 500x. I got pretty good tones by "zeroing my amp's eq" (see below) and running through the amp's preamp. The 4 cable method didn't sound good to me.
My wiring is:
guitar--->POD guitar in----> POD left line out---->amp input 1.
POD's manual switches:
1/4" out = amp
Guitar In = Normal (for strat/tele) or Pad (for LP)
XLR = doesn't matter but I usually leave it on ground
FX LOOP = doesn't matter but I usually leave it on stomp
POD's I/O settings:
Input 1: Guitar
Input 2: Variax (for some reason my patches sound better with this)
Mode: Stack Front
Hot Rod Deluxe Settings:
Volume: To taste
Middle: 6-12 (essentially boosts volume so increase to taste)
Zeroing the amp is really important to get good tones from the POD. Here's how I got my amp's eq settings:
1. Download the tone stack calculator http://www.duncanamps.com/tsc/
2. Select your amp style. If it isn't present you can manually input your tone stack by looking at your amp schematic. (It's a little tricky for NOOBs)
3. Adjust the knobs so that the eq is flat.
4. Use those settings on your amp.
Once your amp has been zeroed, many of the great tones that are preset in the pod can be used live. Just be sure to adjust your A/B volumes in the mixer and choose No cab in the amp settings.