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I would personally go through the vanilla MSQ as it ends with you unlocking the feature of running silos and launching nukes. It involves finding out what happened to Appalachia and the effects of the Scorched Plague; it is the "no NPC" storyline from when 76 first dropped.
It's a RPG. Play whatever missions you want in any order you want. Typically I prioritize side missions so the main quest is easier.
You can play the quests in any order, the actual single player campaign is 60 hours or so. t the end of that you will be level 40+ After that you can then play it any way you like, but the game only starts to open up around level 100. At that point your perks and skills and game knowledge will let you make some more calculated decisions.
This is a big game, 200 hours is when you things will start to make sense.
Most people mistake the Wastelanders story for the "main story", which is best done in tandem with the Overseer's Journey. Completing this story with either the Raiders or the Settlers, will unlock the primary endgame currency, gold bullion. Protip, the final quest for either side is literally called,"choosing sides". Get them both to this point before making your choice to maximize your rewards.
The Brotherhood questline gives you a nice set of power armor at the end, but you buy the mods for it with gold bullion. So that can wait.
None of the other quests labeled "main quests" are really "main quests". They're akin to doing the Thieves guild, mages' college, or Assassins in Skyrim. They're the "main quests" for those factions, not technically the main story.
This isn't too useful though as unless you use the items the sell cost (caps, scrip) won't change based on level.
Some quests reward Power Armor (X-01, Raider, Ultracite, Hellcat) some rewards are unique (Slug Buster, All Rise etc.) and getting them at level 50 can be useful.