First off, I have to say that for some applications, you really can't beat the MFD pickups. They are amazingly articulate, clear, powerful and just straight up amazing for clean tones. I had them in my US G&L ASAT Classic.
Where I was struggling with them was overdrive tones. They work so dang hard to stay clear and articulate, that when overdriven, they tend to get really harsh and some strange frequencies start to happen.
I tried them with my '67 Bassman through a 2X12 cab as well my 18watt Phaez SIBLY (plexi clone) and I just could never get them to work for that great crunchy overdrive tone. I fiddled with pickup height, pole piece height, you name it...I fiddled with it.
I ended up putting a Duncan Jerry Donahue in the bridge and I couldn't be happier. I really like how the JD rolls off just a touch of the extreme ice-pick highs that are typical and they overdrive so incredibly well. It's like a cross between a sweet tele pickup and P90. They just have that great growl that you get from a single coil pickup that has killer low mids.
I kept everything else the same on my guitar, same tone and volume pots and even kept the MFD neck pickup. Both pickups in the middle position sound incredible. I can't recommend the SD JD enough.