Another question one might ask is with such an arrangement with different subs capable of significantly different bass extension capabilities, is where do you set the volume levels? Obviously, regardless of size, they have to be balanced. You may run in to a problem with the small subs on some movies that have very loud and low bass extension that they just can't handle and overdrive them while the bigger subs handle this same bass quite easily. For me, on the surface and in this instance for the goal of obtaining a flat frequency response throughout your room, this would seem to defeat the very purpose you are trying to achieve.
I, personally, have never been a fan of these small subs anyway so my opinion tends to be skewed on the subject. I would go with four similarly capable subs or if there are budgetary constraints, replace the two small subs with one larger one along the lines you described for a total of three.
I have four subs all with at least 12 inch drivers and they handle music beautifully.