The best route would be a tube power amp (such as a Peavey Classic 50/50[discontinued] or a Mesa Boggie 20:20) and guitar cabinet. This will be a more expensive option though. The powerblock option would be a pretty good one, since you would have somewhat of a backup if the modeler died, and if the amp dies you can always run the modeler to the PA. It's a good idea to have two sets of patches for this. One to use with your amp and cab, and one to use going straight to the PA.

My first "big" modeler setup consisted of a Line 6 POD Pro into a Mackie M800 power amp into a Marshall 1960a cab. This worked and sounded great, but was way overkill. You will rarely ever need 4x12's. I can drown out my drummer with my 60 watt 5150 2x12 combo.

Another thing you need to look at is portability. Think about where you'll be using this rig, and how you will get it there.

I know it's not always possible, given peoples location, but try to try out as many different rigs as you can to see which options suit your needs best. Good luck! ;)