In the first Survivor, you learn from a file that Sheena Island, the mass production plant for "Mr. X"-style Tyrants, has achieved this role by making use of a hormone found inside of teenagers' brains, and it's produced when they're frightened/stressed. Umbrella knows maximum fright/stress levels are caused by excruciating pain. Yes, Umbrella tortures kids to death in order to further their goals. Just let that sink in.
Worse, they open their skulls while alive and fully conscious in order to get said hormones.
His diary is even worse, as it reveals that he released the T-Virus on the islandon purposejust as a "Screw You" to the people on the island who wanted him gone. Together with the other entries, it makes him seem even more evil than he actually looks.
The Trashsweepers. Utilizing Uncanny Valley to the extreme, these beings look like Gas Mask Mooks... until they start moving in ways no normal person should move ever. And the hooting...
How about the fact that the Trashsweepers are explicitly described as being one of the lines of B.O.Ws that Umbrella has created? A species of genetically engineered Super Soldiers who have enough intelligence to use pack tactics, operate firearms, and obey orders instead of randomly attacking anything around them. This makes them potentially one of the most dangerous B.O.Ws that Umbrella has created.
The Hypnos Tyrant. It's first form is uncannily human, and is introduced by killing Vincent/Andy/the UT Commander. Its second and third forms are the scariest, however: with an inhuman grimace, monkey-like sounds, and the fact that it's always angry make it a terror to fight. Oh, and it took two missiles from a helicopter to destroy the thing.
The diary entries in this game are Darker and Edgier than other entries in the series but two stand out:
The first is from a prisoner who was kidnapped by Umbrella, and his discovery of their plans and attempt to escape with other kids. This is after you learn that Vincent gunned down escapees from the prison, and the last entry in the diary is the night before that happened.