I would think of something new and fresh, but every time I imagine something like that, my brain snaps back into Legacy of Kain. Come on... focus...
We could go for an AVP type dealie, where you can play the Hunters or the vamps, and there would be two campaigns. Maybe you could even play as Werewolves.
My vampires would be almost illegally similar to Legacy of Kain vampires; The adults would be invulnerable to sunlight, and a lot more powerful. However, Highly concentrated Ultra-violet light would burn. They could probably assume human form once they had reached adult level, but it would not be their default, like in common representation. You would have to kill them by decapitation, sufficient dismemberment and maiming, submersion, immolation or impalement. There would be blooding, a passing down of the condition, in return for sterility. The condition would take hold over time. They would also have different genetic capabilities, like some being suited more to different environments, and having different physical or psychokinetic abilities. There would be a social structure, perhaps even elder vampires. Basically, the vampires from Soul Reaver, but with free reign over the shift between human form and disturbing beast.
Hunter story: You play a middle ages vampire hunter, in the height of the vampire takeover of England. On a hunt to clear out a nest, or settlement or somesuch, and your son/daughter, a training hunter, gets infected(I'm not sure I like the idea of bitten.). You embark on a quest to find the cure for your son/daughter. On the way, you find tales of the losing battle against the vampire infestation, and the battle with the big ol' Vampire would probably involve dark catacombs. However, the twist in the tale is that there is no cure, and your son/daughter transforms anyway. As they transform, you have the option to kill them, but get the bad ending. If you wait until they have finished transforming, and then have a final battle with them, you get a better ending.
Vampire story: You, the castellan of a castle somewhere in England, return from a successful hunt to share the spoils with your subjects and friends, only to find them all dead. Foolish these humans are however, for they have left the head of one vampire intact. You see into his memories, and gain information on the perpetrators of the incident, residents of a nearby settlement. You travel to the village, but since you are only a few vampires, you give orders to your people, and you can be stealthy, or you can be murderous. Maybe there'd be a reputation system. The point is, you find that the Hunters have upped their initiative, and are co-ordinating assaults on vampire strongholds, undermining vampire dominance. So, you have to rally the troops, and force humanity into submission again.
Wall o' text looms, so I'll leave you with that.