How and why is the vampire humane? A soul, or something else? A soul immediately suggests dragging in the old Shanshu prophecy issue, and really needs an answer to what happened to Angel and Spike. Something else should suggest its own problems.

Why was the Seraph exiled? What can they do now? Are there any more of them around, and how do they feel about each other?

What's the Revenant's deal, the witch's, and the ninja's? (Obviously there's the flipping out and killing people, but aside from that...) As a rule, the more you tell us, the more brainstorming we can do.

While I'm very much in favour of starting with the classics, with an exiled PTB among the Cast, a plain old vamp might be a bit low-wattage in the Adversary leagues. Even if they've been depowered completely, they used to bestride the multiverse and now they're dealing with one little vampire.

Adding a stronger vamp subculture is fair enough, but it might not appeal to fans of the setting as-is which shows vampires as fairly little-league, and most of the behind-the-scenes wickedness has been handed over to the (largely) human likes of Wolfram & Hart, and their demonic backers. Of course, that was a source of irony back when they were facing Angel that might be lost with a new cast, and vamps like Russell Winters (from wayyy back in A1.01 City Of) certainly stacked up the influence.
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I'm running a game! Buffy: The Watch House