Erik and James have popped on the forums explaining how they can't sell in big box stores because they're on a different scale of economy.
Not sure if James has chimed in on this, yet (I'm still digging through the thread), but I don't believe I've ever said that we _can't_ sell at big box stores (I assume here you're mostly talking about Barnes & Noble and the like).
Getting in those places is VERY difficult, but is is possible. We publish a lot of "small stuff" with tiny or even no spines, which makes stores like B&N reluctant to heavily stock our books. That said, the Pathfinder Chronicles Campaign Setting has gotten wonderful penetration into Barnes & Noble, and I expect the hardcover Pathfinder RPG Core Rulebook and Bestiary to get significant play in bookstores as well.
Companies smaller than Paizo will likely get into B&N ONLY if they are distributed into the book trade by a professional distributor (really either DBD or PSI at this point), and even then it is far from a sure thing.
WotC, having decades of bookstore inertia from their own efforts, the efforts of _their_ distributors, the legacy of TSR's brands, and the piles and piles of corporate money they have thanks to publishing numerous very successful brands, doesn't face the same challenges smaller companies do when it comes to mass market penetration.*
--Erik Mona
Publisher
Paizo Publishing, LLC
* I'm sure Scott Rouse could tell you horror stories about mass market accounts that we little guys can't even imagine, though, so it's not all wine and roses on either side of the industry.