I have an upcoming project where the subfloor needs major leveling. From the front of the house it drops 3" over 17', then comes back up 1" in the next 13'. Total area is 615 square feet. I have done similar jobs in the past, but never built up more than 1.5", always using layers of plywood. So in this case I'm thinking it will be better (more cost-effective) to install sleepers over the existing subfloor, then finish with 3/4" plywood.

One concern is that the floor will sound different based on the height of the sleeper at any particular point, and especially compared to the area (roughly 40%) that will built up using just plywood, no sleepers. So I'm considering using some kind of insulation in between the sleepers. Problem is that the area to be filled will be 2.25" at the deepest point, and maybe .5" at the shallowest, and sloped the whole way.

Any suggestions for how to execute this method? Or other methods I should consider?

I will be nailing down 5/8"x5" engineered hardwood.

Glue and screw the sleepers with sub-floor adhesive. You could use the blown in insulation made of borate treated newspaper, but you would need to fluff up a bale through a machine you rent at HD. One feeds it into the hopper the other directs a hose. It will compress easily if you put a little too much down.
I'm not sure of the R value, but it's blown between the studs in our outside walls,
and over the batts in our attic.