Anything on TV more widely available than public access is, almost by definition, mainstream. Even the non-mainstream shows are mainstream, their selling point being that they're "non-mainstream."
If a show doesn't make big dollars for the network, it doesn't get on in the first place. Almost everything you see and touch today is mainstream, and if you think it isn't, it's because it's been marketed to you as non-mainstream.
I don't think that's quite fair. Some shows are more obscure than others. I'd use Parks & Recreation as an example of a "marketed as non-mainstream" show. It's not as popular as The Office, sure, but pretty much everyone has heard of it.
Louie is a bit different. Most people haven't heard of FX, and of those that have, most people haven't watched Louie. So while not obscure like "one copy of this book was ever published", it's not "mainstream" like Seinfeld.
Actually, I think if you look at the ratings Comedy Central has more obscure comedies. I am assuming that "non-mainstream" translates to small audience. Keep in mind that while Sunny started out as a cult hit, it's about to become the longest running live action comedy on cable. In contrast, last Thursday The Daily Show did worse than Sunny, The League, and Beavis and Butthead.
And if you compare to broadcast, all of cable looks non-mainstream.
Well, he does have his own show on FX.