I think I'd define mainstream as essentially anything that's physically sold in the Big Box Bookstores... if you can find it at Barnes & Noble's physical stores, it's mainstream.
In terms of books, mainstream seems to only define what is allowed into the traditional sales system that is largely controlled by the big bookstores and the publishers. It is further identified by publisher or promotional materials seen in traditional venues (the stores, newspaper and magazine ads, posters and billboards, etc), something Big Pub can manage whereas indies generally cannot.
Obviously this doesn't include the electronic distribution system, which will let in people (like me) who cannot penetrate the traditional system.
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