I figure I should go with an ABC model for the plot. One A problem (hitting 2-3 PCs directly), one less important B problem (hitting another pair), and some C foreshadowing. Once A is solved, B becomes an A, and C becomes B, and I do more foreshadowing.
Okay, I want:
The client is Elaine Yamaguchi, a graduate student at the university in the cultural history department. Her graduate advisor, Dr Michael Edwards, was found dead just outside his office, and the police ruled it a wild animal attack. However, all of his research notes are missing.
Without his notes, Elaine is totally screwed -- her advisor is dead and all of their research notes are gone. Even if she can get a new advisor, she can't re-do all of her research from scratch. So she wants the PCs to recover his notes, and find out what's going on. A sympathetic detective told Elaine that word came from higher up to put the kibosh on this case, but that if she wanted help she should talk to the PCs, since they have a rep for handling "freaky stuff".
The bad guy is a vampire named Orlando Morvant. Edwards did research into the occult scene in the early 20th century, and when confronted Morvant will claim that Edwards had come into possession of pictures of him between 1898 and 1933, showing him unchanged over 45 years. This is a lie.
Orlando has a goon -- a werewolf named Ulf Wartooth, and a band of unnamed werewolves. He also has a bunch of human Renfields. When the PCs start asking around, he'll send the Renfields to mess them up and warn them off. (This should fail, and should let the PCs do some questioning of the survivors.)
Ulf hates Orlando, but he's a werewolf, and Morvant can command wolves, and so Ulf is pragmatic about it. He has some influence over rats, as well. He'll try to put a whammy on Skuleo to prove what a scumbag he is. Also, when the players go to Morvant's nightclub, Skuleo will notice a wererat he knows (Hector Achaikos) there. If he talks to one of them privately, he'll find out that the vampire put the whammy on him, and he'll learn about Ulf.
Elaine is a Macguffin. She doesn't know very much, but once Orlando finds out she exists, he'll send Ulf to go grab her. After all, she might be able to translate some of the more obscure stuff in the notes.
Once the PCs get ahold of the real notes, they'll find out that they don't have any photos in them. Instead, they are a bunch of ethnographic documents detailing magical practices in the early twentieth century. There are a lot of demon summoning rituals, some of them for demons Nick and Theresa's PC know personally (maybe even for one of them). But vampires can't summon demons? Some of the magical sigils will look familiar to Amber's character, and maybe give her nightmares.
Right now, these two categories are not yet separate.
Anyway, I've got two PCs with the Key of Vengeance against Hell, another one who is some kind of weird Kwisatz Haderach messiah-type, and a an ex-Reaper, and a wererat rights activist.
One by one:
Nick's PC has an "angelic parole officer", which means that Heaven and angels exist, which means that someone will get the bright idea of asking them for help. So I need a good reason why they won't show up and overshadow the PCs. The obvious thing to do is to say that they don't because they can't -- it's against the Rules for angels to intervene in Creation, and our angel is bending them just talking to Nick's PC. This means that there are rules he SHOULD follow, too, and will follow carefully to avoid Falling.
One of them will be a strict refusal to tell anyone anything about the truth or falsehood of any religion; he should have some bureaucratic language like "As per General Orders, Article 12, Section 3, Subsection 4, Paragraph 19, Subparagraph (b), I am not permitted to either confirm or deny any theological fact, theory, or supposition" which he'll then soften by saying something about the need for faith. The model should be Heaven from that movie _A Life Less Ordinary_; it's a bureaucratic place like a divine police station. The fact that this is a somewhat irregular contact also explains why he can't get too pissed off about Teresa's demon, who doesn't have a "parole officer". Morgan Freeman should play this guy. He's a good person with an incredible workload and a very limited ability to directly help the PCs. He can really only offer moral support (though that's something!). For a name, let's call him Hagiel.
Andres's character is a wererat. How are his people oppressed? Well, rats (along with bats, wolves, and cats) are often animals vampires can control, so maybe were-creatures are often Renfields for vampires. And vampires are basically always evil Eurotrash scumbags. Furthermore, the werecreatures themselves can be split with ethnic tensions -- (gangs of) the predator types can want to EAT the wererats.
Amber's character is the product of a secret occult breeding program. Obviously I can rip off the Azrael origin story from Batman, and mix in a bit of Templar fun. A secret order worshipping Baphomet and trying to mess with Jesus Christ's DNA via his bloodline is totally sacri-licious. Also, I can have siblings or clones of Amber's character trying to get her. (Clearly she's the final, superior, version, at least until I introduce Cyborg Clone Ninja Jesus.)
Theresa's character needs some thinking. Sex and violence, sex and violence, hmmm.... Okay, here's an idea, tying into Hagiel. Maybe the angels CAN go after demons, but only ones that haven't been summoned. If a demon gets a sorcerer to summon it, then it's on Earth "legally", even if the sorcerer dies or something. Only straight runaways from Hell can be hunted down. Maybe Theresa's character was summoned and aced her summoner, so she's here "legally", and Nick's PC isn't.
Alex's character is a little oddball. What can I do with an ex-Death gunslinger...?
--- La Cosa Nostradamus ---
There can be a human mob of sorcerers, who are kind of magic mafia -- La Cosa Nostradamus, if you will. To run with the metaphor, the sorcerers can try to "protect" humans, where their notion of protection is to beat down any overt supernatural activity. Basically, they want to prevent magic from coming out into the open, so that they can continue to use magic for power and profit. Also, they will oppose mad attempts to kill millions of people in an effort to become a god, because hey, you don't sh-t where you eat. They can be the bad guys the PCs team up with from time to time, and feel dirty about it. Also, they're probably pretty racist towards other magic critters, just like the real Mafia is towards everybody. They probably think of werecritter/human relationships as a reason to kill people.
--- Vampires ---
Everybody hates vampires. That's because they do whatever they want (as long as it's evil), wear great clothes, live forever, and get to kill anyone they don't like and have sex with anyone they do like. They probably own a mega-corporation, like in Blade.
--- Ninjas ---
--- Demons ---
Demons are like vampires, only worse.
--- Templars ---
We need secret Templar conspiracies. Maybe Amber's character is descended from Jesus, a la the crazy Merovingian conspiracy theory.
Because of the plot, really.
The thin rationalizations for this are that most people have a vested interest in keeping it secret. So when I make up some bad guys, give them some kind of weak-ass rationale. Eg, vampires hate publicity because of torch-wielding mobs. The magic mafia wants to get rich with magic. Angels aren't allowed to tell people they exist because it would weaken their faith. Demons don't want people to know Hell actually exists, because it would make some people change their behavior. And humans put crackpots in insane asylums.
Also, when monsters die they should turn to dust or evaporate or turn into human corpses. Also, make a running joke out of what the news says about the big-ass action sequences.