Like anything "mainstream," it's what the majority of the population is aware of and uses. You can argue over what falls into that category but, for example, the CBS/NBC/ABC networks are clearly mainstream while Daily Kos or Red State clearly are not.
Then, of course, we can decide what "media" counts. Is it just news, or is music and film part of "media?" Technically it is, but people usually refer to "media" as entities informing people's world views and knowledge of the world. But then, people can and do argue that music and movies do that, too.
Ultimately, I think the lines are being blurred as a greater and greater percentage of the population starts understanding how to use the Internet. Blogs and independent news sites are becoming more and more a part of the discourse and meme-circulation. Newspapers are becoming less so unless they move away from focusing on print editions and more to Internet editions, with blog-like features. YouTube, which used to be entirely frivolous, is becoming more of a force to allow people to express world views. I'd say, for example, that any specific YouTube video is unlikely to be "mainstream," but YouTube as a whole is probably pretty close.