There is several endings to the game that require you to complete side missions in certain ways. The "secret ending" is only achievable if a certain NPC is a lot in the positive area, even more than is necessary to unlock that NPCs normal ending. If you don't follow up on two NPC's side missions, those endings are respectively locked out too, or if you don't side with them at the end. If you simply go through the main mission, there is only two endings available to you, if you go through everything in a decent manner you have 8 endings available to you.

Side missions also affect eachother and some have hidden timers, if you don't complete an objective in time or don't check in with the NPC, things will happen out of your control.

Hell, if you manage to play the nomad side missions well and a particular NPC likes how you do things, you can get their gun. But if they don't like you, that doesn't lock you from the rest of the nomad options, you just don't get that gun.

For all the bugs that the game has, side missions and choices do affect things and the game makes a good effort on making you feel like it has more impact than it has (after all, a lot of it is simply a like/dislike score, but a lot of games operate on that scale), like some meaningless inquiry option (ie, blue dialog option) can lead you to a completely new dialog tree that can open up a small side mission in a different way.