Cat does raise a good point about "Azumanga Daioh". Beyond the more enlightened or open-minded "otaku" (I prefer enthusiast, myself), "Azumanga Daioh" essentially has no audience here in the States, which is a damn shame, too, since it's probably one of the best series around.
Action drones will be put off by its slower pace and lack of explosions, shoujo types will be disappointed by its lack of romance, the majority of the US population either wouldn't get it or not even try to view it, dismissing it as a sissy series about girls, and most girls, well, would be turned off because it's not yaoi

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Not to mention a dub would involve massive rewrites if they wanted to try to appeal to more people (thus killing a lot of the series, in the process, more than likely), and probably be atrocious sounding.
And where is the marketing potential? There is none in the US, which makes it less attractive to mass market distributors.
So yeah, there will always be series that will never be shown on TV. I would consider some of the mainstreaming to just be a partial foot in the stream, as it were. Trigun, DBZ, Bebop, Eva, Gundam - all of them (with varying levels of quality) have mass market appeal because they all have action and marketing potential, and are fairly easy to grasp. They'll have their day, then sink back into the less visible mainstream.
I'm out...