OK, my prefered setting for lead most of the time is the Modern High-gain model on the POD, with treble and mids on about 7, and bass on 4, gain on about 6.5, a subtle long delay, and reverb on about 4, supplemented with a DS1 for a little extra smoothness, and generally using the neck PU. At the moment, I'm trying the Holdsworth method; same amp model, but mids all the way up, bass and treble almost completely off, no delay, a tiny bit of reverb, and the bridge PU exclusively. It's wierd, but actually works suprisingly well, so I'll be keeping it for the legato stuff from the Harmonic Major scale I'll be experimenting with today...
Seriously, try it...it would actually be an interesting approach to try in a metal setting.
As a man who cranks his mids on a recto in a metal setting:
You cut through like a motherfucker.