Start as you mean to go on.
The very first Vampire: The Masquerade story, Baptism by Fire, in the first two editions of the rulebook, really set out how different Vampire was intended to be. It centred on interaction with a small cast with no direct conflicts but opportunities for intrigue, romance, philosophical debate and a ringside view of how corrupt and cracked Gary’s Kindred politics really was. It felt, and still feels, a long way from the dungeon.
I remain pretty proud of the arc plot to my first Requiem game, a few years back. It started with the simple notion that the self-loathing vampire who would rather be human and opposes other vampires is usually the star of the show. Louis, Angel, high-Humanity PCs in Vampire RPGs. So what would an antagonist like that look like?
The plot concerned a rise in apparently-Kindred-led attacks on vampires’ holdings, ghouls in prominent places and the like. Who was really behind it?
The leading seer of London’s Circle of the Crone, the Sybil, occasionally noted without comment that vampires are a plague on the Earth, which the players didn’t pick up on as she said a lot of creepy things like that. She almost always prophesied bad news, and this was just assuming the worst of vampires and being proved right almost every time.
So she decided to pull the city’s Kindred society down and wipe out as many other vampires as she could...