Horror is one of the most open-ended genres in all of cinema and every new voice in that world could bring something interesting to the table. While some tropes and stereotypes take hold and gain popularity, there are always reversals of the established orders and weird subversions of tropes.
Horror movies with women in the villain role aren't rare, but the split probably isn't anywhere close to 50/50. Most of the big slasher villains are male, many classic movie monsters are male, and even some non-human threats in the genre are coded with masculine identity. Blumhouse is one of the most prolific production houses in the cinematic world, so if there's a trope to be played with, they'll see both sides.
Sue Ann "Ma" Ellington - Ma
This 2019 psychological horror film enjoyed mixed reception upon release, but it does center on a unique and interesting performance. The story goes that director Tate Taylor and star Octavia Spencer had previously worked together on The Help and Get On Up and developed a longtime friendship. Taylor wanted to make something disturbing and Spencer wanted to break out of her usual type casting. The result was Ma, a horror film about a dangerously unstable woman who manipulates and tortures a group of unsuspecting teenagers. The original script, written by Scotty Landes and picked up by Blumhouse before anyone else joined the project, was set to star a white woman and featured no backstory for Ma. Spencer's performance is the beating heart of the film, it would be a complete mess without her holding it together, and she makes Ma a memorable villain.
Dr. Zoe McConnell - The Lazarus Effect
This supernatural horror film takes notes from classic stories and fails to find much to do with them. Despite substantial box office returns on a tiny investment, critics were brutal towards this tepid PG-13 horror effort. Its centerpiece is Zoe, a scientist working with a team to find a chemical solution to death. She and her team succeed, but an accident leaves Zoe tragically slain. Overwhelmed with grief, her fellow scientists use their serum to bring her back and seemingly succeed. Unfortunately, Zoe quickly evolves past her capabilities, develops incredible psychic powers, and becomes inexplicably cruel and violent. Zoe tearing through her former friends like a comic book supervillain is the most enjoyable aspect of the film. She's believably scary, uniquely creative, and inarguably powerful. Zoe is the best part of The Lazarus Effect, and she frankly deserved better.
Grace Ferrin - The Purge
The first entry in the overwhelming Purge franchise is better remembered for what it led to than for anything that happened during its runtime. The concept of an annual holiday during which all crime is legal was clever, but it took a few films for the franchise to make good use of it. The first film focused on the Sandin family, a group of rich suburbanites who find their mansion fortress assailed by preppy murderers. After laying their lives on the line to protect a homeless man and losing the family's patriarch in the process, the Sandins kill the home invaders and believe themselves to be safe. That's when Grace shows up. Grace leads a small army of the Sandins' neighbors, fed up with the family growing richer off of their money and determined to kill them for it. Grace represents one of the film's themes, as unsubtle and obvious as the others. She's a living representative of the hatred and jealousy that animates suburban living in some communities. She isn't in the film for very long, but she's a key part of what The Purge has to say about its social experiment.
Lola - CAM
One could and should argue that the real villain of Daniel Goldhaber and Isa Mazzei's 2018 horror film CAM is the callous and unacceptable way many treat sex workers. The film's actual villain is strange, as CAM tells the story of an ambitious camgirl named Alice who discovers suddenly that her account has been taken over by an exact Doppelgänger. Alice discovers that other women on the site have been replaced. Lola isn't properly explained by the narrative, but the eventual confrontation is a unique exchange. CAM is one of the most bracing and interesting films in Blumhouse's recent output.
Laura Barns - Unfriended
More notable for its filming gimmick than its plot, Unfriended is a strange experience. The simple story sees a Skype chat between five friends haunted by the ghost of a peer that they bullied into suicide. Laura is an unusual presence in the film, only briefly glimpsed in person, but it's her wrathful vengeance and cutting manipulation that drives the plot. The audience doesn't learn much about Laura Barns beyond her tragic death, but her ghostly actions make her a unique and interesting villain. As the film goes on, more is revealed about the main cast that paints them as more guilty than Barns herself. Unfriended is a unique spin on the vengeful ghost trope.