Kris, since Audyssey tries to equalize the irregularities caused by room effects for the main speakers as well as the others, sure it may be of some help with just them playing.
Your question seems to imply that you use only the mains when playing CDs and other 2-channel music sources. Using modes such as DPLII to extract the ambience naturally present(to varying degrees)in 2-channel material and send it to the surrounds where it belongs(the majority of sound in the hall reaches the listeners as reflected ambience from a direction other than the front)is preferred by many, including me.
