Just do whatever you want, go whereever you want. I played over 1000 hours since release (this is double time to skyrim, 5x fo3, 5x fnv for me), and in every new playthrough i see things, buildings and stuff, i never saw before. If you enjoy building i recommend using homemaker and build th sh** out of the commonwealth. If you enjoy exploring, just go explore, maybe play on survival for that extra thrill, use "adjusted encounter zones" if you like even more thrill. I highly recommend to get cait, curie Hancock and mcreedy to play their quests. What i do in most playthrougs is: - join Minutemen, conquer the north and build some stuff. - from graygarden on, join BoS and do some quests - after coming to goodneighbor or diamond city, try to join the railroad - do all kinds of things - eventually join the institut and do some things for them - do more things for RR and BoS - conquer every settlement and build stuff, shops, make fortune - and finally, have fun