Tom Holland’s Spider-Men counterparts both experience betrayal and loss by way of good friends. Holland has not, and no, Mysterio doesn’t count.
Very few are unfamiliar with the story of Peter Parker and Harry Osborn, best friends since childhood.
Things go south between the two friends, and Harry dies -- or, in the case of The Amazing Spider-Man, kills Gwen Stacey and is kept in an asylum for the criminally insane.
It's a lot to take in, but the storyline works. Nothing hurts a character more than having their best friend turn on them, then try to murder them.
The Tobey Maguire and Andrew Garfield Spider-Man films, it was not just their best friends, but evidently, every friend they made that ended up wanting to hurt them in some way.
In every one of Tom Holland's Spider-Man movies, the only "best friend" who betrayed him was Mysterio.
The latest installment of Holland's Spider-Man franchise, Spider-Man: No Way Home, included a funny scene during characters express how they experienced friends betraying them.
This resulted in Ned Leeds, played by Jacob Batalon, looking rather shocked and making a promise to his own best friend that he would never betray him.