Daniel, M22s supported in the low bass by a good sub or subs cover the entire audible range in a superb fashion. One area where the M80s could play louder would be the upper bass(say about 80-200Hz)where they have two 6 1/2" drivers compared to two 5 1/4". However, the M22s can certainly cover this range with enough volume for nearly all home use.
If you use two subs the maximum benefit in smoothing overall bass response is had when the subs are separated(your comment about not enough "room" implies that you may be thinking of placing the speakers and subs all close together)in certain locations. Typically this would be at the midpoints of the opposite sidewalls or front and back wall or in diagonally opposite corners. If you can place the subs efficiently, M22s plus two EP500s would serve you very well.
