Nature? Divine. Human nature – toxic.
Humans are the dominant species of Earth, gifted the soul by God some point after coming into being. Humans are considered God's greatest creation, however their favor would draw the ire of Lucifer, who saw them as flawed and murderous things. The view of humanity among the rest of the Host of Heaven varied, some like Castiel saw humans as works of art, while others like Uriel saw them as lower beings, referring to them as "mud monkeys" and "savages" and comparing them plumbing on two legs, beliefs Castiel warned were close to blasphemy.
Throughout the years, Sam and Dean have encountered threats they believed to be supernatural, only to find that they were dealing with a completely human culprit. A fact which Dean frequently would comment on, revealing his disgust at the lengths people will go for to hurt others, calling them "sick" and "crazy", seemingly preferring the simplicity of actual demons and monsters.
The Winchesters first encounter with a human threat were the Bender family, consisting of patriarch Pa Bender, brothers Jared and Lee Bender and the youngest -- Missy Bender in Hibbing, Minnesota. The Benders would kidnap a man by the name of Alvin Jenkins while taking out the trash on night, leading to Sam and Dean arriving in town to investigate the disappearance, due to John marking the area as a possible hunting ground for a phantom attacker based on local folklore.
When Sam gets abducted, Dean teams up with a local deputy, Kathleen Hudak, whose brother went missing three years prior under the same mysterious fashion. When Alvin is set free, he attempts to escape, to Sam's protests that it a trap, but is caught and killed by Jared and Lee. After finding the Benders home and locating Sam, Dean goes to find the key to free him, but is captured soon upon entering the Bender home. While restrained, he learns that the Benders hunt humans, but plan to kill Sam in his cage. When Sam gets free with the help of Deputy Hudak, they take out Lee. When Pa and Jared go to check on him, they are able to incapacitate both men, while Dean freed himself and locked Missy in a closet.
In the aftermath, Deputy Hudak confronts Pa about her brother and asks why they do what they do, only to get the cackling response, "because it's fun." Horrified Deputy Hudak takes her gun and shoots Pa, killing him.
After reading about a man, Bill Gibson, being murder in a locked room, Dean and Sam head to Stratton, Nebraska to investigate a possible haunting. When they arrive to the house they find the Carter family moving, and pretend to be building inspectors, and urge the family to stay at a motel for a few days. The family disregards Sam and Dean's suggestion and move in. Later that night, the family is attacked, prompting Sam and Dean to enter and tell them they are dealing with a spirit. However, when a the "Girl in the Wall" crosses a salt circle, they realize they are not dealing with a ghost.
Learning that Krissy Chambers is being trained as a hunter along with other teenagers by Victor Rogers. It soon becomes apparent that Victor was behind the deaths of Krissy, Aiden and Josephine Barnes' family members, with the help of the vampire Seth, so Victor can mold them into hunters. When Victor is confronted, he attempts to escape with Seth, but is stopped by Krissy who prepares to shoot Victor. As Sam and Dean try to talk her down, Krissy pulls the trigger, only for the gun to dry fire, with each pull of the trigger Krissy tells Victor is for each of their families that Victor destroyed. A distraught Victor sobbing on his hands and knees on the floor, pulls a gun from his sock holster. Before anyone can get to him, Victor puts the gun to his head and pulls the trigger killing himself instantly.