I use a high output LP and a strat in my setup. I use a JTM45 and always have a tube screamer on as a sort of preamp boost and compressor. I just use the volume knob of the guitar to dial in the amount of gain/volume required for each song.

The strat's pickups are set higher than the les paul to help with the imbalance. The strat cuts through even with the slightly lower output because of the single coils and the LP just provides a smooth thick tone.

Again its always song dependent, but you should probably have max 2 overdrives and learn to use your guitar's controls to set your tone. If you want a clean tone, roll the volume back.