I think people may be wrong when they say the big publishers don't care about this. Remember how all of the big publishers jumped into casual games? And into social games? Yeah, there was some big money going around (especially in the latter), but they won't ignore stuff like this, either.
But while I like to characterize it as a kick in the butt / smack in the face to the big publishers, it's not that, either. You have to realize how these guys play ball. They are big and cautious (duh!). They let others take the risks, watch carefully, and then swoop in with their money to either buy out or clobber the survivors.
I don't think they are going to see this as a trend, yet, however. More of an anomaly. Now if people like Charles Clerc and Jeff Vogel and Thomas Riegsecker and yours truly all start getting stinking rich alongside the InXile crew making these kinds of games, THEN you are going to see movement from the big publisher front. They'll tell each other that "the market has changed" (because, you know, it wasn't that THEY just couldn't be bothered to make decent games to address a substantial niche… it's because the market didn't exist until they started paying attention, of course). And THEN you are going to see a hell of a lot of old franchises getting dusted off, because jumping into what is now an unfamiliar subgenre with a "new" franchise is just too risky.
And there are maybe a few who are seeing another pillar of the game-publishing industry - financing - starting to shiver. First it was distribution, now financing… they still have marketing, but if I were a bigwig at a major game studio I might be either planning for a shorter horizon on my personal exit strategy if I wanted to leave triumphant, or start figuring out a way to reinvent my company.
We could be in for some interesting times. But I wouldn't start counting my chickens just yet. But I've no doubt there are several high-level managers right now who are paying attention to the Double Fine Adventure and Wasteland 2 bids with interest.