I've noticed that killing innocent civilians while he's your companion can make Preston hostile. So how is one supposed to complete the main storyline if you've alienated the other three factions and then made it so that Preston attacks you on sight?

You can't. Maybe next time, don't be so homicidal

So much for the Minutemen being a failsafe

If you sleep for a day or 2, companions would cool down and cool with you again. You can talk to him to initiate Minutemen ending. That's why you can't kill Preston, he's the failsafe ending.

Well heck. Preston is just too darn forgiving

You are saying this to the guy with a stalin quote in his sig. (Albeit a good one, but still.)

As Battlebloodmage said, just get away from him for a day or two and he'll forgive you. The reason he can't die is because he's your only way of beating the main quest if you managed to piss off the Railroad, the Brotherhood of Steel AND the Institute.

Just kill him. No great loss

Easiest solution, if you go on a spree, don't take Preston.