The Hangover, Wedding Crashers, and 40 Year Old Virgin are some of funniest fucking movies I've seen in recent years and they were all mainstream. Amelie went pretty mainstream (more so than some of Jean-Pierre Jeunet's other films) and it is a fantastic film.
Agatha Christie is one of the best selling authors in the world (she's like up there with The Bible and Shakespeare),and the best-selling mystery novelist EVAR, and I love her books.
Same thing with some music - there are mainstream bands which are fantastic, and others that suck.
What I watch for is a lot of extreme commercialism...that's what is wrong with "mainstream" sometimes, is the commercialism behind it, the lack of content, blah blah blah...but that doesn't mean that mainstream in and of itself equals bad.
Unless you're a pretentious hipster and a band is only good if fifty other people have heard of it.