The Humbucker Secret
Bare Knuckle PG Blues - I have these in a PRS Custom 22- just awesome!
Ok, I really didn't know that this was a secret but apparently it is.
You get the greatest range of tones, and dynamics when your humbuckers aren't nailed at 10.
The caveat of course is that you want to hear everything which probably means you aren't playing death metal or running your signal through a chain of Metal Zones or whatever. If you like that sort of thing, go for it, but the secret won't matter to you.
No matter what kind of amp that I plug humbuckers into, I set the amp volume with the volume pots on the guitar no higher than 8. Some guitars have better volume pots than others so your mileage may vary as it will depending on how hot the pickups are. The hotter the pickup, the more you might want to dial the volume down for maximum tonal range and complex overtones. For example, on my 335 with Lollar Imperials or the 355 with Bare Knuckle Stormy Mondays, setting the volume knobs at about 8 really deliver incredible range. I have an older MusicMan AXIS Sport with really hot pickups and for that I roll the volume off between 6 and 7 if I want the maximum tonality.
The body wood also matters and while I know that there are folks who say that body wood does not contribute to tone in an electric guitar, all I can say is you're doing it wrong. Since you don't have a lot of room to wander in the wood, we spend little time on it here.
With single coils, the output is typically less strong and so you probably will not find this secret makes much of a difference, but if you have stacked singles or noise reducing singles, there's another magnet in there somewhere and the secret may fit for you. I have an old Fender Eric Clapton "Blackie" with Lace Sensors and it is one of those guitars where rolling off the guitar volume and lifting the amp a bit does make a difference. Mind you, those Lace Sensors and the rest of the electrics are headed for the bin now that I have received a new set of pickups mounted in a scratchplate with new electronics from Tim Mills at Bare Knuckle.
Back to your humbucker equipped guitar. If you want to see if you can get more out of the instrument you have, there's no harm in trying out this little secret. The worst thing that can happen is that you don't hear a difference. My experience with good pickups into a nice tube amp or into a Kemper then into the DI, I do hear a difference to the positive.