In 1864, she stopped and fed on the passengers of a coach showing Damon, before he was fully turned into a vampire, how it is done, taking sadistic pleasure over the coachman being so concerned about the safety of a lone lady on the road at night. She wickedly smiled at him, thanked him for his concern and then fed on him, clearly showing that all humans were to her, was food and amusement at that time. However, it is known that even then she could find humans as potential mates. It is a fact that she had a sexual relationship with both Salvatore brothers and eventually turned them both and saying to Stefan that she loved him as she was being carted away to be presumably entombed in the Church. This is likely an exception since she hasn't shown any concern for human life even of the opposite sex presently.

In this century, she used Isobel Saltzman as an agent in her plan to destroy the tomb vampires in Mystic Fallsmost likely knowing full well Isobel's cold disregard for human life and her willing to use them to murderous ends. She was first seen in the 21st century when she kissed Damon while dressed as Elena Gilbert, letting him think she was Elena. She also let John Gilbert think she was Elena as well until she hacked off his fingers and stabbed him with the intent to kill him. She was interrupted by Elena entering the house and finding him. As seen in The House Guest, she is drinking human blood from a hospital blood pack without killing humans.

Katherine and Elena.

As Elena called 911, Katherine reappeared behind Elena unseen by Elena despite John's gasped warning. She didn't kill Elena or reveal herself to her but toyed with her using her super speed. However her attitudes toward humans haven't changed. As a bait to create a crisis between the Salvatore brothers and herself after Stefan rejected her, she deliberately smothered Caroline Forbes in her hospital room, a human that did her absolutely no harm, knowing that she had Damon's blood in her system.

However, while she has no regard for human life she doesn't care for her fellow vampires either. She admitted to Stefan Salvatore that she betrayed the Mystic Fall vampires in 1864 by making a deal with George Lockwood, the son of the mayor of the time and a werewolf, ostensibly the vampire's mortal enemies. In exchange for covering up his own attacks on humans, Katherine allows him to blow the whistle on the town vampires so he can increase his standing in the Mystic Falls founding families and in his personal family. She did this so she could be rid of her personal enemies among the vampires and fake her own death. It was him who arranged to have Katherine escape the tomb in exchange for the Moonstone, which at the time Katherine had in her possession. This shows a ruthlessness that demonstrates she is out solely for herself, despite the fact that she cares about Stefan.

Katherine's ruthlessness and indifference to others is likely due to the fact that her family disowned her for having an illegitimate child (at the age of 15), and later on were murdered by Klaus. Her daughter is the only person Katherine has been shown to truly love at a significant degree, even though she still had at least some feelings for her family, and she was carried away only seconds after Katherine gave birth to her. Even when she first met Klaus and Elijah, she still believed in love, and even had a short moment when she bonded with Elijah, due to Klaus being elsewhere and told him "if we cease to believe in love, why would we want to live?" Later on, her entire family was brutally slaughtered by Klaus as revenge for her having eluded him. Both events left her completely devastated, contributing to her reasons for turning off her emotions. Also the fact that Klaus wanted to use her as a sacrifice for breaking The Sun and the Moon curse didn't help matters, making her all the more bitter and distrustful. She is an example of a tragic villain, which is a character who, although acting for primarily "evil" or selfish goals, is either not in full control of their actions or emotions and the reader or viewer can sympathize for due to them not being evil by choice; but rather by them being a victim of circumstance.