This isn't so much a movie as it is a ninety-minute work of film criticism. Whedon and Goddard are talking about the horror genre, from the final-girl myth to the torture porn craze to the cultural differences in horror movies in different countries to the question of free will and agency in victims to (as Nordling at Ain't it Cool points out) our own culpability as fans. And you get most of that in the first ten minutes, let alone the first half.
That said, I suppose if I do discuss anything specific, I should toss in a spoiler tag. A few discombobulated random thoughts behind the cut.
One of the best themes in the movie is the dehumanizing of the victims, something that dates back beyond Hooper's Texas Chainsaw Massacre (although that seems like the obvious starting point). Whedon and Goddard establish the core five characters are real, non-archetypal people (even weed addict Marty is way more than a fool), then shows them literally being chemically altered to behave like they're "supposed to," with the need to create The Whore out of a perfectly normal woman being the most notable bit (between the chemicals in her hair dye designed to make her stupid, and the pheromones released as she and her boyfriend wander outside).
Meanwhile, we also get the folks back at the evil corporation (which is also humanity's only hope) taking bets on what evil creature the kids in the cabin will release. Amy Acker lets the security guard know that they're not cruel, they're just blowing off steam. And, of course, they are. These people have the jobs of satisfying the demanding
The double-dehumanizing effect of the horror film -- on killer and victim alike -- has an obvious parallel on the effect on filmmaker and audience, of course.
But that thing I said above about the movie just being a work of criticism? Not so. Those dehumanized characters remain all too human -- whether in the cabin or the lab -- and the script is just too damned fun. The final act, in which the various beasts promised on the betting board are revealed, is glorious beyond belief. Demonbats? Unicorns? Aliens? Clowns? An "Angry Molesting Tree?" Who can't love a scene like that?
And then there's that awesome ending. No deus ex machina. No wimpy happy ending. When confronted with how fucked up the world is, the only logical response is, "fuck the world."