Prometheus -- fighting back against the gods
First, I'll get the film's one major flaw out of the way. The basic premise -- that the Engineers created humanity and that's why our genome is identical to theirs -- is impossible. The human genome shows us to be members in good standing of the Earthly biosphere of millions of species -- our genome differs only slightly from that of our fellow great apes, by a bit more from that of other primates, by a bit more from that of other mammals, etc. If, as the film implies, life on Earth was "seeded" by an alien visitor, the vicissitudes of natural selection would not, billions of years later, produce one species genetically identical to the original. Alien intervention in human evolution is a plausible SF premise, but humans being genetically identical to aliens is not. In fact, if we discovered extraterrestrials genetically identical to ourselves, the only possible conclusion would be that they were somehow an offshoot of Earthly humanity, not vice-versa.
That being said, it's clear that this film, like the original Alien, can't be taken entirely literally. If you look at it as an exploration of mankind's relationship with its creator (assuming the existence of such a creator), it becomes much more interesting.
The question the expedition sets out to answer is why the Engineers created us. In one of the film's better exchanges, the android David (the most interesting character, despite Peter Weyland's pointed comment that he lacks a soul) asks Holloway, "Why did your kind create me?" Holloway shrugs, "Because we could." David replies, "Imagine how disappointed you'll be if that's the only answer they have for you." The religious premise that, if a higher intelligence created us, it must have done so with benign intentions, is thoroughly eviscerated here.
Shaw's religiosity didn't bother me because she never lets her superstition get in the way of her humanity and pragmatism. She's on her way to meet, for all practical purposes, God -- humanity's creators. But when she finds that those creators are militaristic brutes with a huge arsenal of thoroughly nasty weapons of mass destruction, she doesn't offer bovine pious acceptance, she declares "We were so wrong!" and starts fighting back. In the film's most gut-wrenching scene, she emphatically refuses to serve as Mother Mary to one of the nastier creations of the "god-like" Engineers, using every ounce of her ingenuity and endurance to abort the monstrosity. When the last surviving "god" sets out to bring Judgment Day to mankind, it's Shaw who urges Janek to thwart him.
Indeed, the theme of humans fighting to the end for human survival repeatedly recurs. Holloway, at first a rather bland character, willingly invites a horrific death to avoid infecting the rest of the crew. Captain Janek is a jokester and a flirt, but when called upon to give his own life to save the whole Earth, he rises to the occasion, grimly at first, but without hesitation. Even Weyland's quest for personal immortality is noble by contrast to the thuggish "superior" being that casually murders him.
The Engineers, in fact, are the real monsters here. Once one gets over the massive disappointment of their human form, they actually embody the ugly side of humans -- brutal and muscle-bound, cold and indifferent. It's not surprising that they set out to destroy humanity. It's more surprising that they created us in the first place, but the Engineer who did that might well have been a dissident from his own kind (recall that Prometheus was a god who brought down fire to humanity in defiance of the other gods). My guess is that when Shaw reaches their home planet, she'll find that there, too, they long ago wiped themselves out; after all, the military base shown in the film had lain undisturbed for two thousand years after the Engineers there were destroyed by their own creations, which makes little sense unless their species as a whole had suffered a similar fate.
There are (what I interpreted as) nods to other SF works. In particular, the mechanism that enables the explorers to see images of events from the distant past, guiding them to the actual corpse of a being whose death they "witnessed" in that fashion, reminded me of the "spieltier" in Barton's Alpha Centauri. Better-read viewers will doubtless spot further allusions.
Yes, there are some minor flaws. It's not clear how Shaw and Holloway deduced from the pictograms that the Engineers created humanity, as opposed to merely visiting. Some characters are oddly careless around nasty-looking alien creatures. Vickers is arrogant but not stupid, and I couldn't believe she would die simply because it didn't occur to her to run sideways as Shaw did. The scientists don't really act or talk like scientists -- but movie scientists rarely do.
Set against this, there is great visual spectacle, real drama, and real ideas. Prometheus has the spirit of Alien and Aliens in this sense -- our species is capable of greatness and beauty, but so far from seeking out a benign Heavenly father, we must struggle and sacrifice for survival in an ugly and hostile universe.
Some other worthwhile reviews: Roger Ebert, Glenn Kenny, Chris Picard. Film discussion site is here.