I just watched it with the commentary, and they (director Kirschenbaum, lead Askew and co-star Nash) stay pretty tight-lipped about it, as well as other elements. At one point, though, the director says (about the flashback killing) that they never openly discussed it, and it's best left up to the audience's interpretation.
I got the feeling that the flashback killing was some accident involving Joe & Alex a long time before the events in the movie. In the opening scene, Alex asks Joe if he told Liz about "it", and he admits yes. Note how the mystery killing flashbacks are always in b&w while all the other flash-forwards are in color. I'd say b&w scenes represent things that occurred before the movie timeline.
From the b&w flashbacks it looks like Alex was on the ground, possibly getting beat up by someone, and Joe saved him by shooting the attacker. After Joe fires, we see Alex get up, mouth bleeding, and spit on the body. My guess is it was a random brawl that got out of hand. But it establishes the bond that Joe & Alex have, the way Alex "owes him one" and seems to be Joe's protector throughout the film.
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