Hi RubberSoul! I have had to experiment with this a lot, and from what I have found every combination of guitar and amp is different. The best thing might just be to try everything!
Not that I am an expert or anything, but I usually start with everything on the amp at 5 or whatever the middle is, and the volume and tone on the guitar at 7 or 8. From there you can play with all the knobs individually to get what you want.
Often with humbuckers I end up dropping the mids to make the clean tones sound nicer, or you may find that you like a more mids-forward sound and boost them. I think single coil pickups can sound harsh at times, especially with distortion on, so experimenting with the treble or the tone knob on the guitar (which takes out some of the treble) can help. You might even find that rolling the volume on the guitar down not only reduces the volume but also takes some of the highs out. The volume often has a tone-effect with it too. I like to keep the volume at 7 or 8 so I can roll it up to get a little more distortion whenever I like - that's kind of fun.
There are also EQ pedals out there too, as well as pedals that doctor your signal in other ways. Infinite possibilities!