Guitar: Tone knob all the way up. Neck pickup for leads and solos. Bridge pickup for power chords, pinch harmonics, and twang. A mix of both pickups for rhythm and textured melodies.
Amp: Try playing around with the knobs. There is no right or wrong way, but start with the bass knob and play an open E chord or some bass notes and roll the knob until you hear a noticeable drop/increase in the response. That's the sweet spot. Then try the mids with an A chord or Am pentatonic scale, look for the sweet spot again. That should get you started.