here's my takes on the new questions raised:
the beginning obviously raises the question of why that engineer was seemingly the only one on earth and why the hell would he do that to himself, but i don't think that is a question that even needs answering.
the goo is a biological tool, not necessarily a weapon. it may be an infectious agent that affects the dna of the hosts and as it replicates picks up their traits and seems to be some kind of xenomorph precursor. it seems to have some viral mechanisms such as incorporating itself into dna. and like many viral infections, there are specific times when it is infectious, which i use as a sort of loose explanation as to why shaw gets a weird spermsquid baby and not an exploded head. as the infection progresses you get the symptoms of holloway and the engineer in the opening scenes - you fucking fall apart. holloway's just took longer because he had less than a drop of the stuff and the opening engineer drank a whole glass of it. when you fall apart in the right conditions to support life (ie earth in the opening scenes), the mutated dna goes about its business and continues to evolve. (also i'm not sure that the engineer in the opening is necessarily seeding ALL life on earth or just the origins of HUMAN life) when you fall apart in an inhospitable planet, vickers just flamethrowers you.
i guess when you have mutated sperm this is a particularly hardy and rapidly growing thing which is really just the result of the infectious goo biotool rapidly evolving its hosts' characteristics. the resulting giant squid alien is probably the equivalent of a xenomorph arising from a sperm. there are references to the xenomorphs in the movie when milburn and fifield mention that there are bodies in the pile that have been opened up from the inside. couple that with the fact that we see some form of xenomorph come out of the engineer at the end and the fact that the engineers are genetically similar to humans, that might mean that a similar event happened on the engineer vessel, resulting in a xenomorph outbreak that killed everybody.
what happened to the xenomorphs (or whatever killed them) after the outbreak? who knows, it's a big moon and it was a long time ago...they probably starved to death after killing all the engineers or something. whatever happened to them, it's clear that they were around prior to prometheus landing there, since they're on the murals in the tomb. as to the specifics regarding the differences in the tomb and the cargo hold, who the hell knows, who are we to judge some ancient alien religion? our religions and their weird rituals are incomprehensible enough as it is.
what's david's motivation for infecting holloway? i don't really see this as a plot hole...he's an ambiguously intentioned character, we don't know who he was speaking to via the visor (or how many communiques they've had), maybe there are W-Y bigwigs back home who want some kind of bioweapon. i suspect his plan was to infect holloway and bring him home in cryosleep to bring the weapon back, but when that failed he found a surprise back-up in a pregnant shaw. this sort of alludes to alien, where ash is ordered to return the alien to W-Y at the expense of the crew, and also to aliens, where burke wants to infect ripley and newt and bring home an alien in cryosleep because of W-Y's desire to use it as a bioweapon. perhaps it's the events of prometheus as relayed by david to W-Y execs that give them this idea in the first place. i think david has some sort of secret corporate agenda that not even vickers knows about, but when weyland's play at eternal life just gets him decapitated and the only way home ruined, he has to alter his plans on his own. or maybe it's simpler, and he's just curious, or just a jerk.
why doesn't anybody notice an alien spermsquid hanging out in the medical bay? for starters, that was vickers' private medical bay. the rest of the staff seemed to have a different medical bay and no access to that surg-o-matic tube. david knows what happened but i figure he just assumes that shaw has managed to kill the thing. i chalk it up to bad writing that the chronology is so messed up and hard to understand, but all of this seems to have happened pretty quickly so i suppose it's understandable that nobody really noticed between the confusion of weyland actually waking up from cryosleep and zombi-fifield murdering everybody.
zombie-fifield is probably my biggest gripe; i don't understand how he got super strength/agility/invulnerability from having acid and goo on his face. he was really just kind of a cheap plot device to kill off a lot of people at once.
anyway it's far from a perfect film, but i think the script and its pacing and various plot holes and cheap devices were probably the main offender. i think it fits the mythology of the alien universe pretty well, and overall i thought it was entertaining as hell. after one viewing i can't say i hold it on the same level as alien/aliens, but i think it shits all over alien 3 and resurrection, and don't even get me started on the avp movies. it's got its flaws but i think those are flaws in the script and storytelling, not in the backstory. i don't think it's deserving of the majority of the backlash it gets regarding where it fits in the universe.
/reallyoveranalyzingthingshere