We (the human race) killed an Engineer (Jesus) that was sent to Earth 2000 years ago to "correct" our course, that made them decide to destroy us as an ultimate solution.
(The answer contains spoilers but due to the fact that they are in various places, I decided not to mask them)
There is an interview of Riddle Scott (which you can read here) where he actually addresses your question.
What he says is that the Engineers created the life on Earth and watched us closely over the course of the human history. They visited us by time to time but they didn't intervene.
By the time the human race reached the bottom of its decadence (which according to the director was during the Western Roman Empire) they decided to "reason" us by sending an Engineer to Earth who was what we now know as Jesus Christ. What we did with him? We crucified and killed him.
That was the catalyst that triggered their reaction to return to Earth and empty all their "black substance" cargo. They believed that if they cannot correct our path, then we didn't have a "place" in the universe and our objective has been completed. They set a course to Earth to destroy us but their plan backfired on them when the substance contaminated and killed the crew of the exact ship the team of Prometheus visits in the movie.
If you watch carefully, Dr. Shaw carbon-dates the decapitated Engineer and says that "he was killed 2000 years ago, give or take". The Prometheus expedition takes place in 2091, so give or take 60 years (Jesus died when he was 33), that makes a lot of sense.
There's a great deal with God and religion generally in the movie, also. Dr. Shaw keeps wearing her cross and even though all the western religion philosophy is disestablished from a specific point in the movie, she defends herself by telling that some greater being must exist that made the Engineers:
-Guess you can take off your father's cross now.
-Why would I wanna do that?
-Because they made us.
-And who made them?
Elizabeth talking to Charlie about their DNA findings
An alternative scene that was deleted from the theatrical version, also explains that the Engineers come from a place that is called Paradise, the name that the majority of human religions give to their heaven.
-When that thing, ripped your head off... What did he say David? Where did they come from?
-Thing, Dr. Shaw? Not too long you considered them gods.
-God never tried to kill me.
-So, David? What did he say? Where did they come from?
-There is no direct translation but several of your ancient cultures have a word similar to it. Paradise.
Elizabeth asking David what the Engineer said when he talked
So, the Engineers that created us in the first place are the same ones that decided to destroy us. And they have a very good reason to be upset!
P.S.: Guess how more upset will they be in the next movie (Alien: Covenant) when Elizabeth will visit their planet wearing (guess what!) her cross!