Two Subwoofers... Comb Effect

I think it's an advantage to place the subs as close to the mains as practical running in mono to minimize phase issues. There is going to be some overlap of frequency and you don't want the same frequency coming from sources several feet away from each other. Speaker makers go to alot of trouble to align drivers. Depending on the crossover slope it might also be beneficial to angle them within 15 degrees or so of the mains. Yes it's all room dependent and you could end up with something quite different but I would start with the sub drivers and the main drivers on the same plane as close together as possible with a similar angle. In a normal sized room treatments are likely to be needed - Jim

A reason to place stereo subs as close to mains as possible is the inevitable "leakage" of sound above the crossover level. On paper, a driver contributes 50% to overall spl at crossover frequency and a sub continues to "roll off" above from there.
Listen to your system with only the subs powered up, don't even need an spl meter.
All that "supra-sub" content from the subs would seem to affect imaging, etc. the least by such positioning, though I've not done subjective testing. My stereo subs will stay where they are - immediately adjacent to each main speaker.
A Velodyne SMS-1, Rives PARC and other of their ilk will do a reasonable job smoothing peaks to make the nulls less toublesome at one's listening position.

One key is to keep the x-over as low as practical. This will make sure you can't localize the bass. My Maggies, 1.6s are x'd-over at about 40-45hz. Seamless and invisible.
Phase, however, is another matter and does make a difference.
I wish I had a fully variable 0->180 control rather than the 0 OR 180 I now have. Small point, but don't forget that sound travels at about 14"/millisecond, so a small movement of the sub can produce phase changes, too.

Thanks Todd,
That Harmon International link is not only interesting....it is the first quasi scientific documentation that appears to prove that multi subs are the only real way to go.

Sorry....I meant thanks Duke!