I agree with ShieldWife. V:tM using just the corebook negates the metaplot and instead, you can keep the conflicts and NPCs local. Metaplot sells books, but its rarely useful for actual play. The only NPCs who matter are those who interact with the PCs. The issues of the wider world are mostly just background. Think Batman and Gotham.
As for involvement with mortals, that's easy enough to create on your own and tailor it specifically to your local setting and the interests of the other players. Mortals should be a constant threat yet vampires should be drawn to them for more than just food.
I've played and run Nightbane and Werewolf much more than Vampire (which I mostly LARPed), but the concepts are similar. One of the best things I did as a GM was have the PCs be tied to the mortal world through their past mortal life. I got this heavily from the Spawn comics. Spawn may live in a dumpster and battle angels and demons, but he also has to protect his ex-wife, his daughter and his blind grandma. And of course, various elements of his "human life" get caught up in the various supernatural threads as well. It's especially fun when you have a mix of dumb, cunning and smart mortals.
Also, the fate of the mortals and the town/city has to matter to the PCs...for whatever reason. Like superheroes, the monsters of WoD are the protectors (though Vampires are both protector and predator) because the whole point of playing an anti-hero is you are a bad thing, but you fight worse things.