The pickups in this particular setup could definitely get muffled. Issue was that there was no happy in-between zone that I could find while playing. I use my tone and volume knobs a lot in a given night and it was all like - too bright - too muffled - way too muffled - too bright again - too muffled. Even when the treble was reduced, there was something really strange sounding in the mid-range that you couldn't get rid of with the tone pot. There just wasn't any happy middle ground on the pot that I could find where it was 'just right'. Treble bleed probably wasn't helping things either.
In general I'm not a fan of radically re-eqing an amp to suit a guitar. All of my guitars sound different (strat is bright, 335 is darker, etc) but they're all set up (via pickup swaps and wiring) to work well with pretty similar settings on my amp. With the 500k pots and those low output singles I was having to turn treble and presence off and the mids and bass way, way up. And although that was closer to fixing the brightness issue the amp overall then started sounding weird.