I try to approach it as logically as possible, asking myself questions like... Will anyone care? Do I care? Will it all sound shit anyway once pumped through a PA? What is least likely to cause problems? etc etc
I've found overtime that no one gives a shit what you use as they aren't at a show to investigate the nuances of guitar gear. So it falls to what I want personally.
I hate having pedals on stage (I move around alot), so the AxeFX dealing with all that helps. MIDI patch changing is a game changer if running with clicks. If I'm on the other side of the stage and it's time for a solo, the patch change happens automatically. However, I like air pushing on stage, so I have a power amp and small cab on stage behind me with the output from the AxeFX minus Cab Sim.