I agree Dave, its hard to know for sure.
My sense from the description is the problem is early portion of the main.
Could be in the timing too.

My suggestions:
Note the vac, rpm, AFR at interstate cruising speed. (ie 65 mph)
Compare with same at county highway speeds (which will be less throttle) such as 35 and 50 mph.

If the metering blocks have 3 or more "emulsion holes", plug two of them. A little too much air early in circuit startup can make it go rich-lean-rich.
Keep the one near fuel level and one near the bottom open. They should be around .026-.028" dia.
If they are really small, then 3 e-holes can work. I think Dom or Mark have posted sizes that can work with three holes but don't recall if that was for 4150s or dominators.
The three hole Holley block I got from QF had 3 holes around .028" dia. I plugged the middle ones.

Note: As throttle is opened from steady cruise at highway speeds, the AFR should go leaner and the vehicle should accelerate (in other words, power output increases).
A lot of us grew up thinking more throttle makes more power by making a richer mixture but its not true. Only when near full throttle does it need to go richer.