I've played modded Skyrim for 500+ hours in one playthrough - with few quest mods, mostly immersion mods - and still haven't done Dark Brotherhood questline or Dawnguard questline.
I think 400+ hours without doing everything is entirely possible unmodded in Fallout 4, assuming the town creation & defense is as engrossing as we hope.
I think 400+ hours without doing everything is entirely possible unmodded in Fallout 4, assuming the town creation & defense is as engrossing as we hope.