I recently bought TC Electronic NOVA SYSTEM and NOVA DRIVE to complete my POD HD500/DT50-212 setup in live performance. Although pairing POD HD500 with DT50-212 is supposed to be the “dream gear” as publicized by LINE6, I ended up having poor guitar sounds in live mode on Disto/OD side. AMP modeling is great but some effects sound "weak" and I didn't like the overall result.
After trying many pedal boards, I decided to go with TC Electronic gears as they sound great, are easy to setup and, last but not least, are fully MIDI compatible.
NOVA SYSTEM drive section is OK but does not offer as much possibilities and doesn’t sound as good as NOVA DRIVE (NDR-1). Placing the NOVA SYSTEM in POD HD500 loop mode using NOVA System LINE IN input bypasses the DRIVE section.
First 2 weeks, I used only DT50 without POD (controlling DT AMP with this layout) but I really missed being able to switch from Twin Reverb to MESA BOOGIE to HIWATT or Marshall simply by pushing a button.
The other thing was having cables running from devices to AMP (Guitar Input, Effect send/return), which can become annoying on stage. Putting back POD HD500 in setup allows me to run short length cables between devices and having a single AES-BUI XLR type cable to connect to the AMP. It also allows me to have volume pedal AND 2nd expression pedal (WAH, VoiceBox, etc) that is not offered with NOVA System.

Regarding NDR-1 (NOVA DRIVE), you connect NOVA SYSTEM MIDI out to NDR-1 MIDI IN. In MIDI menu of NOVA System, you can select PGM CHG to be sent to connected device. Selecting Preset on NOVA System will automatically change selected preset on NDR-1. Note that both devices are set to the same MIDI Channel (4).

Basic POD HD500/DT-50 preset: COMP + WAH or VOICE BOX + PRE-AMP (no CAB, no MIC) + Noise GATE + Volume Pedal + Effect LOOP

If you're not using NDR-1, you can use POD HD Distortion pedal models. They sound great, As long as you stick to those, your AMP sound will be a blast.

NOVA SYSTEM MIDI CC control values and Program Change ARE NOT preconfigured, so you must assign parameters prior to controlling the device with MD.
Now, have fun controlling your NOVA SYSTEM, NOVA DRIVE, GR55 and HD500/DT50 devices with MIDI Designer.