Not really. The gameplay doesn't really encourage it since there's a lack of skills. Since everything is about perks you can just keep leveling and be a melee, gun, energy weapon, heavy weapon master all in the same run. The story also barely deviates, and when it does (towards the end) it really just boils down to Kill Our Opposing Factions Then Here's An Identical Ending.
You could maybe do a melee run then a ranged run, but other than combat it doesn't really differ. It can offer 100+ hours if you really take your time, but it gets dull quickly. Once you hit like level 30 your a god of death that can typically one shot Legendary Glowing Deathclaws. Eventually you get the best mods which means your materials stack up quickly, removing the need to collect junk anymore. And once you hit the space cap for a settlement you can't build more (unless you mod that or something).
It can provide a lot of hours, but Bethesda has seemingly been focusing on encouraging one single long as fuck playthrough over multiple so that they can boast about the amount of content they have.
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