I usually use a three step setup method:
In the first step, I deal with the main speaker acoustics only.....measurements and tweaking, until I get a fairly smooth freq response, and with a smooth rolloff (no large peaks/dips)
In the second step, I deal with the subwoofer acoustics only....same as above, measurements, tweaking, ect
In the third and final step, I am simply bringing the two speaker systems together, to join as one integrated system. This is the hard part, and where crossover points, filter slopes...and maybe some tricks, and trade offs begin.
If I've corrected most bass problems, in steps one and two...that only leaves the unexpected compounding problems to correct, as the two systems interact in the room.
Some small amount of EQ'ing could help here.
My room is fairly large, my speakers are planer types (Apogee Duetta Signatures)...and my subwoofers are large monopole cone types (VMPS passive subwoofers)....integration is top notch. As a matter of fact, I've "never" had anyone pick up on the fact, that the subwoofers were in play...they always think it's the Apogees speakers only.
Dave