JoJo's Bizarre Adventure - 1 Gyro = main cast

spoilers to 1-7
Araki seems to consistently kill 3 of the main cast, huh…
Jonathan, Zeppeli, Dire
one of Joseph's teachers, Caesar, Stroheim (resurrected with GERMAN SCIENCE)
Iggy, Kaky, Abdul
Shigechi, Cinderella, Josuke's grandpa
Narancia, Abaccio, Buccellatti
FF (several times), Weather report, everyone but Emporio but then everyone is still alive and well in alt universe after Pucci's death
Gyro, Diego (twice), Hot pants
Josuke's memory, last bits of sanity, Kira Yoshikage

Special mention for Part 1, though. As Araki himself said, killing off the main character was unthinkable at the time, plus it's the only Part to really end in the main character's total defeat, since Dio doesn't die, as opposed to Part 6 where most everyone died but so did Pucci. Part 6 is still the saddest, though, especially since it was going to be the end of JoJo originally, whereas Part 1 was always going to be the start of much more.