The opening of the movie, where most people complained of being confused, is indeed confusing. Yes, the main characters are introduced - and as Alien(s) usual, they all start by waking from cryo-sleep (save the intros of the archaeologists) - in a confusing manner. Where did they all come from? There's a quick explanation that The Company hired some of them on as regulars (the captain, etc), but others didn't really know what they were doing there. Were they kidnapped? Did they show up at a job fair, got drunk and were Shanghaied into service? Doesn't really make sense, and this was a problem that set the other big problem in motion: many of the characters were there just to deliver lines and had no depth at all. That's kind of a bad failing from Ridley Scott, as his other movies do not have this problem.
With that lack of character development in general, the tone and certain specific characters get a lot more time and energy to develop. Obviously the main character, David, and Vickers, but also the ship - which, if you've paid attention to Alien and Aliens, gives you a clue as to what kind of movie this is going to be. I always thought that the Nostromo was a truck - strong in utility but no way to defend itself (just like the characters). The Sulaco was a military ship: very powerful, but ultimately powerless against the ravages of the aliens. The Prometheus is a ship of scientific inquiry, much like the Enterprise (although completely unarmed) - its purpose is to find out the why's in an innocent manner.
With the generally weak character development (save the exceptions), you don't really care so much about the "red shirts". There's a few you don't even know the names of, and that's a huge contrast to the other movies. It also means you care less if most of them die, which takes a lot of the fear/suspense out of the film.
Here's the other issue: this movie isn't Alien/s, and it wasn't meant to be. It's a completely different animal, and when you bring in preconceptions as to what it's going to be, it winds up disappointing big time. There were lots of homages to both Alien and Aliens, but this one tore away a lot of the mystery of the first two films without adding a lot more mystery that you'd care about. Why did the Engineers develop this bio-technology to create and then destroy, only to not destroy after all? Most theater goers probably didn't care - I didn't. If you don't care enough to find out, it kills the impact of wanting a sequel. Alien did an absolutely fantastic job of introducing all this mystery without ANY answers, making you want to know more. Aliens brought some closure to that, but the origin story was left untold - plus, what ultimately would happen to Ripley and Newt. This ending didn't have that sort of hook.
A minor point: the dialog was light and without real strength. You didn't ponder what people were thinking, and no one tried to really convey much conflict.
Here's what was gold:
David. Fassbender really, really stole the show here times a million. Where there was uninteresting dialog, I hung on his every word - anything to give away his true motivations. Where some characters were flat, he was menacing in new and interesting ways. I can see now why Bishop had "behavior inhibitors", and not because of the physical violence malfunctions like Ash! If this film was told from more from his perspective, I would have been on the edge of my seat, but I think it'd probably be a bit too cerebral for wide appeal.
Also, rooting for the sociopath doesn't feel right no matter how cool they are. A friend of mine said he didn't have any feelings towards any of the characters and didn't care if any of them died. I would. If they killed off David, I would have been pissed!
The ship was freaking cool and big-industrial like Ridley likes it. The concept of biological destruction through gross mutation was also a great angle - if also a disgusting one.
I totally missed the plot holes people keep talking about - honestly, I don't see them. To address the ones I've heard of:
* Why does Vickers have a male-only auto-surgeon? It's not for her, it's for Weyland - duh!
* How can someone do all that running and jumping after abdominal surgery? They can't. I agree here as I couldn't suspend my disbelief. Ask any woman who's had a hysterectomy.
* With the above, even on painkillers she'd be so wiped out she couldn't run and jump like that.
Anyway, despite all the opportunities wasted and dialog problems I still very much enjoyed the movie. I hope they don't make a sequel and instead work on Bladerunner prequels or expanded world stuff. Alien(s) is now, basically, completed.