Here's an idea: How about a colonial America in a universe where colonists have discovered that the new world is filled with all kinds of supernatural entities? Lycanthropy and vampirism are just seen as exotic diseases although more dangerous than malaria.
The story starts in a puritan village next to this werewolf forest everyone is afraid of. There has been a series of violent murders and we see things from the perspective of this young woman, we see the village and characters and the horrible stories they tell their children about the vampires and werewolves and witches. It has a sort of 'The Witch' / 'The Village' vibe. However the town's paranoia grows and this woman is caught in the crossfire and used as a scapegoat. She is forced to escape through the werewolf forest. However her husband to be (who she doesn't really like but who defends her) goes after her with his men to prove her innocent. (He may go after her a few days later, maybe it takes him some time to gather his men?)
She ends up being attacked by some werewolves but saved by another and taken to a cabin. This one looks different from the others. Instead of a huge wolf its more anthropomorphic. She has a conversation with it in human form the next day. His name is Tom and he explains as he is cooking breakfast for her that he is a former slave. He is surprised that a full blooded white female human would be wandering about the forest. Two more characters come in (in human form) and apologize. At first our protagonist doesn't understand why, but as Tom explains, these two nice men were the werewolves hunting her earlier.
At this point a few things are established: - Werewolves are not the monsters she was told. They are very dangerous when they first turn but over a period of years can learn to control their blood lust. This forest is a sanctuary for doing that. - You do not need to be bit by a werewolf to get the disease, there are many vectors (like mosquitoes), but most people who get it do it as children after a fever. Tom was just a small boy when he first turned. His mother left him to attend to her duties and came back to find him in a corner, crying, naked, surrounded by blood and body parts. He had killed the owners of the plantation, his father and siblings, and many other slaves. He was friends with the plantation's owner's daughter (although he wasn't really supposed to be, and he doesn't get a chance to kill her). Years later she comes back to hunt him but by that point he has some measure of control and doesn't attack her, even when she demands it. She eventually captures him and instead of killing him she tells him she's taking him back as her property. They eventually develop a method (probably through meditation among other things) of gaining control of the werewolf form and transforming at will. Tom is a werewolf hunter but instead of killing them prefer to take them back with him. He's also a vegetarian. - Our protagonist's puritan village is rather cult-like and she doesn't realize that not all societies view werewolves as evil. Like slavery before it, the issue is split between the states. Tom intends to bring our protagonist to a military outpost run by a general who sees Tom's werewolves as a valuable resource for construction and war. I like the idea that like in Pleasantville this storyline ends to, of all places, Tom defending himself in front of the state supreme court.
Our protagonist's shitty husband finds her and sparks some drama, nearly getting himself killed. He is the one who has a conversation with the eccentric general and gets the backstory on the outpost, learning about the young united states' plan to use werewolves to expand the frontier, including taking away territory from Mexico and more territory away from Native Americans. As a sign of good faith to the people of the Salem village, he is sending Tom back with them to sniff out the werewolf responsible for the killings and bring it to justice.
So the protagonist and her would-be husband have a bit of a reconciliation. He's still and asshole and internally pissed that his friends died so that he could end up saving someone who didn't need saving at all. She's pissed because her village lied to them and she didn't really want this arranged marriage anyway. Internally she feels guilty because as she tells Tom, the past few days (despite their horror) have been the most exciting thing to happen in her otherwise boring life.
They are both deeply uncomfortable with bringing Tom with them, especially the would-be husband. But in a character building moment he decides to put his fear of ridicule aside because he knows Tom is their best bet for identifying the source of the killings. Predictably, the members of Salem are not happy being interviewed as witnesses by an African American werewolf who claims government authority over the autonomy of his investigation. There have been more killing since the protagonist left, which fortunately clears her name. But the towns people are getting more desperate, gathering people under a full moon to see if they turn, performing summary executions of others.
Through careful investigation, Tom reaches the conclusion that these mutilated bodies aren't the work of a werewolf at all, it's a creature killing on the full moon and masquerading as a werewolf. We eventually discover that it is a vampire in the form of an orphan boy who recently moved to the village. This is our protagonist's favorite student and one who spoke in her defense initially (they're all pretty pale here). She tried to help one of the victims, another student of hers, who was already dead. She was found over his body, covered with his blood, which was why she was accused in the first place.
Tom and our protagonist eventually track down the beast and stumble on to this kid in the middle of feeding. He's crying, actually sobbing as he feasts on one of the corpses. He hates what he is. When he sees Tom and our protagonist he hesitates for a moment, perhaps allowing himself to be killed. Tom is pointing his revolver at the kid and knows he should fire but he hesitates as well. Seeing the kid hunched over, covered in blood, and sobbing gives Tom flashbacks to himself as a child after he first turned. Tom allows the kid to run off, which infuriates the husband (the kid does eventually end up murdering again because of this). However Tom explains that this kid isn't evil, and wonders if there's some way he might be saved. Our protagonist also deeply cares about this student (they had some really cool interactions at the beginning of the story) and wants to find a solution.
In the end the vampire kid is captured by Tom and brought back to his cabin / hideout. But in a bittersweet twist our protagonist ends up getting killed. The story then focuses on Tom and the husband as they have their own stories and more characters are introduced. Including the woman who captured Tom and initially taught him.
- Transforming (at will or otherwise) from a human to werewolf is always painful, but stopping yourself at a certain level of anthropomorphism or scaling back is even worse. Those who spend the years necessary practicing enough to control these abilities just get used to it.
- The second story arc should focus on the military base and their plans to take control of more Indian territory as the husband begins his own story arc. Secondary storylines involve Tom imprisoning the vampire kid and keeping him alive, as it was what the protagonist wanted. Also that priest character is introduced.
- At one point we do a bit of a parody of the Witcher in the second season: The vampire kid sees him load up silver and non-silver bullets, and asks "Silver for monsters, lead for people?" He says "both for people." The premise is kind of a Witcher-ripoff.