#2
Whatever you choose to do, I'd suggest turning the mids up more than normal. That's what'll give it the cut to pull through the rest of the mix. Usually, I prefer a smoother tone for leads, but that's achieved through use of the neck pickup. Mids are essential, in my mind, to a good lead tone. Personally, I usually do something like bass 1 o clock, mids 3 o clock, highs 3 o clock, whereas my regular tone is closer to bass 3 o clock, mids 1 o clock, highs 3 o clock.

Also, roll back on the gain a bit to give your sound more definition. Nothin sounds worse than a lead with so much gain it oozes and blurs the notes together. In my opinion, at least.
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#3
I agree with the suggestion to cut back on your gain. Especially on Mesas, you don't need as much gain as you might think to get a heavy tone, especially if you're EQ-ed well.

Try cutting back on your bass, and having reasonably high mids. Treble should be pretty high as well, but I don't like it to be quite as high as the mids.