I have a Spider2 and 4x12 cabinet, and once I got through with looking at others serttings, and threw out what I used on other amps, I think I found my idea of the famous sound (with good humbucker):
MAX, 5 o'clock
I have the STOMP/PRE-AMP turned on as well as the NOISEGATE.
For a single coil guitar, I would increase the drive, turn bass up to 3 o'clock, maybe 4 depending on your pickup. IF it is a little too strong for you, back down the Channel Volume a click or 2.
Good luck with those, I didn't like the CRUNCH model, either red or green, never got it to feel right for the EVH sound.
My biggest issues was I first tried to use settings that worked on other amps. Once I got fed up with the settings not sounding like they did before, I started from scratch and found what I wanted. I have learned that for Line 6, don't apply what might be the right settings on other amps, play with the settings from scratch until you find the sound you want.