Two Subwoofers... Comb Effect

I think it's an advantage to place the subs as close to the mains as practical

That has been my experience too. I fear one can get caught up trying to even out the room modal response and lose "transient" response if you move the subs too far from the mains. In a sense, time coherent bass with the rest of the response may be as important as getting rid of the room modes - in practice I use a bit of give and take....I move the sub out into the room a bit in front of the mains but not so far as I feel that transient response suffers. This leaves me with perhaps less than optimal "room modes" but I am streets ahead of the situation with sub in the corner and still get reasonable transients.

FWIW: If you have freestanding speakers then you may not notice this effect - already free standing speakers are sending bass in an omnidirectional pattern - so you lose bass impact from quarter wave rear wall cancellation from the get go ( a set of nulls in the bass across the entire length of the room).

I ditto the experience with sub(s) placed up near the front of the room, with the mains. Either multiple subs in one location, perhaps just off center on the front wall - near the center - , or similar, or subs near the mains, perhaps in stereo, maybe mono, depending.
It's almost always easier to get a better blend, even from multiple seating positions, and still maintain excellent cohesion from the subs to the mains, from the listing positions. It also eliminates any potential for hearing "voices" from your subs, overlap problems, and just plain integrates easier in my opinion.
While I think, carefully done and considered, you can build an excellent system around subs placed around the room, I think the benefits of doing subs up near the mains offers better integration and benefits - especially when you consider today's DSP and EQ technology applied!
Also, I don't personally like to see subwoofer sitting around the room. The gear is an "eye-soar" as it is, mostly. I'd rather be able to have the option to hide the mains and subs behind some facade if I so chose, in a custom set up. And this is all easily done with all the speakers up front, and side/rears hidden, somewhat. But, that's me.
Still, I can't argue with the excellent results I've had over the years with either one, or all of the main/front subs (usually rears crossed over to these subs also) up front. Clients have been ecstatic to!
Still, in each application, you likely will need to "tinker", and adjust for maximum results, and keep a balance.
Bottom line though, is the results is all that matters

If you have a steep-slope lowpass filter (24 dB per octave), then you can get away with spreading subs around the room. Most subs have a 12 dB per octave lowpass filter, and so will give away their presence and not blend well because they allow too much lower midrange energy to pass through. Since the ear localizes by arrival time as well as intensity, it makes sense to me that if the subs are passing audible lower midrange energy you'd either want them close to the mains, or farther away from your listening position than the mains, or both.

Since the low-pass driver is phase-lagging relative to the high-pass driver, I don't see any theoretical disadvantage in the bass region to having some of the subs a bit closer to the listening position than the main speakers - provided the above recommendation regarding crossover slope is observed. That really is a crucial aspect of a scattered multisub setup, in my opinion.

Duke

4 th order crossovers just never sound quite right to me despite the obvious theoretic advantages of 24db LR. Less overlap and summing to zero at the crossover as well as being able to crossover higher and not localize them. As a result I'm crossing over lower than I might otherwise. As far as the subs being a BIT closer or further away than the mains Duke is right in most real world situations but audible/non localizable frequencies ( 20hz-100hz) if they are in the crossover range will be arriving from two different sources at two different times. This of course may not make a pennies worth of difference in any given situation with any given listener - Jim

Most subs have a 12 dB per octave lowpass filter, and so will give away their presence and not blend well because they allow too much lower midrange energy to pass through.

That is what I have - 12 db/octave. That may explain why I prefer it up front.