The entire narrative of "JoJo's Bizarre Adventure" is a chain reaction sparked by the Stone Mask. The central conflict that spans over a century is the feud between Jonathan Joestar's lineage and Dio Brando. A major twist is that Dio survives the end of Part 1 by severing his own head and attaching it to Jonathan's body, effectively stealing the Joestar bloodline's physical form. This is why he and his descendants can develop Stands, directly tying all subsequent conflicts back to Jonathan's final sacrifice.
In Part 3, "Stardust Crusaders," the secret to defeating Dio's time-stopping Stand, "The World," is the revelation that Jotaro's Stand, "Star Platinum," possesses the exact same ability, a one-in-a-million occurrence that allows him to move within the stopped time and ultimately defeat Dio. The main villain of Part 4, Yoshikage Kira, is a seemingly ordinary serial killer who gains a Stand that can turn anything into a bomb; a major plot turn involves him using another Stand's ability to change his face and identity completely, forcing the heroes to hunt for him all over again. His Stand later evolves to create a time loop, "Bites the Dust," to protect his identity.
Part 5's "Golden Wind" reveals that the mysterious boss of the Passione gang, Diavolo, has a split personality, with his alter ego being the timid Vinegar Doppio. His Stand, "King Crimson," doesn't stop time but "erases" it, allowing him to predict and avoid any action. The finale sees Giorno Giovanna's Stand evolve into "Gold Experience Requiem," an ultimate ability that can nullify any action or willpower, trapping Diavolo in an infinite loop of death for all eternity.
The most significant spoiler is the ending of Part 6, "Stone Ocean." The villain, Father Pucci, a disciple of Dio, succeeds in his goal of accelerating time to reset the universe. In the process, every main character except for the young boy Emporio is killed. In the new universe, Emporio manages to kill Pucci, breaking the cycle. This act finalizes a new reality where the souls of the fallen heroes are reincarnated into new people (like "Irene," who replaces Jolyne) who are free from the fated Joestar curse. This controversial ending serves as the definitive conclusion to the original universe and the Joestar-Brando saga, paving the way for the rebooted universe of Part 7, "Steel Ball Run."