Sure, right up until you hit the (several) points where you try to do stuff that seems like sidequests but don't become available until after a certain main quest. Like everything involving Nick Valentine (and by extension the entire Far Harbor DLC) for example.
This is not an argument for the game's story structure being good, as presumably the OP will not be using an alternate start mod on his first playthrough. The ONLY mods I recommend for first playthroughs of these games are the unofficial patches.