Misfire at cruise, popping/afterfire at 3000RPM

Hey FABO -

I've been trying to solve this issue on my own for a couple months now, but I think I need help. I have a 440-6BBL that idles nicely, but presents with a random but frequent misfire at a light to moderate cruise. At 3/4 to WOT, the misfire gets much worse and the engine begins to stumble, pop, and backfires through the exhaust (afterfire). Here are some details to get started:

440-6BBL
UNKNOWN CAM
BLUE ECU FROM HALIFAX HOPS (THANKS!!)
NEW 4 PRONG RESISTOR
MAG PICKUP DISTRIBUTOR W/ VAC ADVANCE CONNECTED
STOCK TYPE COIL
AUTOLITE 85 PLUGS GAPPED TO .035
NEW TAYLOR 8MM PLUG WIRES
NEW BATTERY
CARTER HIGH PERF MECHANICAL PUMP
FUEL PRESSURE REGULATOR SET AT 5 PSI
92 OCTANE
OPEN HEADERS (SAME PROBLEM WITH FULL EXHAUST)

12 MMHG AT IDLE, NO COMPRESSION TEST OR LEAKDOWN PERFORMED YET. 20 DEGREES INITIAL, NEED TO CONFIRM TOTAL. FLOATS ADJUSTED IN THE CARBS.

IDLES NICELY, MISFIRE AT CRUISE. BAD MISFIRE, POPPING, AFTERFIRE AT 3/4 TO WOT. WILL NOT REV OVER 3000. DOES THIS BOTH UNDER LOAD AND REVVING IN NEUTRAL IN THE DRIVEWAY.

I've checked for vacuum leaks, but that doesn't mean there's not one I'm missing. I've adjusted the timing as far down as 10 advanced, but the engine doesn't like that at all. 14 advanced and it will idle, but roughly. I ended up at 20, and anything over 20 advanced doesn't seem to make a difference. So far, I've pulled the #1 and #6 plugs, and while they look a little rich (to me), the ground strap is pale and almost straw color. I'm going to pull the rest a little later, but pulling plugs on a 440 with headers is easier for me if I'm under the car.

Today I plan to check the reluctor gap, but I need to pick up some brass feelers.

The problem feels to me like an ignition problem, because I had this issue before rebuilding the carbs and it remains. The issue also remained while driving with only the center 2BBL connected and the outboards blocked. One possibility I can think of is maybe the vacuum secondaries aren't opening under heavy throttle, causing a lean condition. That's another test I'll perform. All throttle blades move freely, nothing hung up. I've disconnected the fuel line from the pump going to the carb to ensure ample fuel flow. What are some other troubleshooting jobs I can do?

Apologies for this being so long, I wanted to cover as much detail as possible right off the bat.