Hey zekester, I would definitely recommend running the outputs of your POD to the line inputs on the Scarlett. Use the POD for all your effects since that's what it does best, and leave all the audio input and output to the Scarlett. It has nicer preamps and generally I find Focusrite to be a step above most companies (including Line 6) in terms of writing device drivers. Make sure you have your driver type set to ASIO in Options | Preferences | Audio and pick the Scarlett as your ASIO devic so you're using the Scarlett to its full capacity.

As a side note I've found with some multi-effects units that running them direct into an audio interface changes the way many of the effects sound. I had a Zoom unit that sounded great running into my amp (Fender Reverb Deluxe '65) but when I ran direct into my DAW all the effects sounded awful. It was most noticeable on the distortion effects. Eventually I figured out that adding an amp/cabinet emulation at the end of the signal chain made a massive difference, honestly it was like night and day. Not sure if your POD will have the same problem or if it has amp emulation but it's something to watch out for. You could also try adding amp emulation on the software side with a program like Amplitube or BiasFX which are great options for those of us who favour one physical amp (Fender for life) but would like more options in production.