It is no secret that the vast majority of characters who appear in the MCU are based on characters from the comics. Sometimes it is their name; sometimes it is their appearance. Sometimes an entire character's personality and backstory are imported; sometimes it is very little, leaning toward a mere Easter egg. A major pastime of Internet fandom is attempting to predict when the comic characters will finally make an appearance and how their traits and backstories will be modified.
What I am interested in is which characters are entirely original creations for the movies (and 2021+ TV shows). This may be a little liable for opining, but I think some objective arguments can be made. For the purpose of this question, the most "major" characters means ones that appear the most or have the most tangible impact on plot.