Ask the players where their characters get their blood from. Really make them think about it, especially if the PC in question has no business hanging around fingering hoboes or picking up prostitutes. Do they have a trusted servant who bares vein for them twice a week (paid overtime for the pleasure, of course)? How does the servant feel about this? Above all, what would happen if that safety net of regular, planned, safe feeding was taken away? This is always a good plot to break out if the PCs don’t create one for themselves, or in the lull while you frantically work out how the hell the local Tremere are going to react to having their chantry filled with lawn ornaments or what the Toreador primogen thinks about having her childe’s illegal blood doll left in her conservatory with a note saying “people who live in glass houses can’t throw stones”.
When designing NPCs advise against feeling obliged to include every clan (in the old Vampire) or every rank within a covenant (in the new Vampire): you’ll end up with everyone being a chief and no-one being an Indian. The important NPCs are the Prince, the Prince’s Enforcer, a couple of entrenched elders and a couple of ambitious up-and-comers, plus a few people for all of these to order around (if you’re running a Sabbat-centric game like I did, this converts into the Archbishop and/or several Bishops, a senior Priest and a couple of rival packs). You really don’t need to worry about every clan having its primogen or every covenant having all six of its ‘board officials’.
I would advise GMs (especially of the original Vampire) to have tangible bloodlines extending down from any Methuselae that happen to be around (because a fourth-generation vampire doesn’t just sit on its fangs for three thousand years… well, not very often, anyway) and up from any PCs of the same clan (because tying the PCs to Important People makes the metaplot personal, and making the metaplot anything other than a narrative piledriver is crucial if you want anything to do with it). Even for Requiem, it helps to ensure some links between members of a clan – vampires don’t travel well and so two Ventrue in the same place are as likely to share an ancestor as not. If they don’t, there’s a plot point there for interested players to snatch on and uninterested players to ignore (as is their right – don’t force it on them, just have it there as a thing, and remember, it’ll be more of a thing if it’s their character’s clan and a character they, the player, are interested in).
Make sure that some of the NPCs are just flat-out more powerful than the PCs, that some are far more socially important than them and have friends or powerful allies who’ll notice them being gone, and some of them are important to the PCs somehow. Vampire society is inert and stagnant – people are killed and overthrown, but it doesn’t happen every day. The weight of centuries bears down on these creatures and getting rid of one should take effort. If you’re into your tactical challenge gameplay, consider the strategic challenge of getting rid of someone who has all the odds on their side. It’s up there with dragon-slaying, I swear.
Once you’ve started running… this is a game about being a vampire, so make sure that people are aware of what that’s like. Keep track of PCs’ blood usage. Remember they consume blood just in waking up, and will likely burn through a whackload in every fight they enter – but don’t make feeding feel like recharging a battery or something offhand like that. If you want the characters’ vampire nature to be fairly central to things, make sure that it’s ever-present but subtle. If a character’s hungry, they can smell passing humans, and it’s intense – like the smell of a roast dinner when you haven’t eaten all day. That drunkard with the red face is like a glass of mulled wine on a cold evening. Something you want. Something that’ll make everything that little bit more bearable. Don’t let them get away with swaggering through the streets of London swilling down prostitutes left, right and centre. Don’t tell players how their characters feel, but do stimulate them to feel something.
People have five senses. So do vampires, and theirs are often sharper. Paint broad strokes with some, fill in details with one or two, and if you really want to be creepy, take one away. If the characters can smell and taste the London Peculiar (that’s ‘fog’ to the uninitiated) but can’t see or hear jack, they’ll be weirded out. Remember, it’s the World of Darkness; nothing is entirely what it seems to be. The decrepit bookshop is the front of the Tremere chantry’s underground laboratory. The prosperous premises of St. Katherine’s Dock hide Giovanni merchant necromancers whose waterlogged cellar is full of ghosts that can’t be seen but can most definitely be smelt. Salisbury House looks like a fine limestone edifice, a house of the nobility, but there’s always the thick, heady smell of incense emanating from the ground, and they’re always looking for new servants. Tie sensual details into plot points and you won’t go far wrong.