this topic is mentioned a lot, but the key terms are always switching, so it's hard to find a good sample post...

The main thing I think you need to consider the quality of the cab/mic sims, especially for metal, if you want to go the active loudspeaker route.  I have found they are a bit lacking for high-gain, but have found a method to improve upon them, by using "dual cabs".  I discuss this here:

http://foobazaar.com/podhd/toneGuide/cabsMics#dualCab

Note, this uses dual amps, which takes up quite a bit of DSP.  If you want to use a full 8 effect chain, it's probably not possible using dual cabs.  You may not have much more room than a Distortion, EQ, and Reverb, and you probably can't use Spring Reverb.  If you like to use the Pitch Glide or Smart Harmony, you probably can't use Dual Cabs.

For single cabs, I'd try using the Hiway, XXL, and PhD cabs.  I'd turn down Res. Level on the Hiway but boost it on the XXL/PhD to get a good sound, and use either the 57 on, 57 off, or 409 Dyn mics.  Single cabs can be made to sound good, but I find I need "dual cabs" to sound great.

Using a real poweramp and cab, you won't have to worry about all this, but the downside is that you have less versatility - you only have one power amp tone and cab tone to work with.  If you're only looking for a few tones, using the Pod almost like a 3 or 4 channel amplifier plus effects pedalboard, then you'll be happy with this route.  If you want to emulate things from Van Halen to Meshuggah, you may prefer the active loudspeaker route.

anyway, either way has pro's and con's.  I'll refer to the real amp/cab route as "live" and running to a active loudspeaker/PA as "direct".

"Live"

Pros: Probably better tone, more traditional guitar rig aesthetic, can explore options not provided in the Pod (4 cable method on an amp not modeled in the Pod, different cab choice)

Cons: More stuff to lug around, got to change tubes every so often (if you get a tube power amp), only get one power amp/cab tone (although the Pod's "live-voiced cabs can expand on this somewhat), have to mic your rig for louder gigs which can take more time or be a pain to get right, subject to speaker directionality

"Direct"

Pros: convenient to carry/setup, have more versatility with amp/cab/mic model choices, no speaker directionality to worry about, no retubing to worry about

Cons: onboard cab/mic sims probably aren't as good as a real mic'ed cab, not a traditional aesthetic