Besides talking Maurice Bernard into retiring and the Who Killed Drew murder mystery!
I'd have some some sort of natural disaster, like floods (I would say wildfire, but that could be traumatic for viewers and actors alike), to help reset the show and get rid of the riff raff...
Then these stories:
-Gia had a child by Nikolas that Helena kept hidden all these years. Trina meets him and they fall in love without realising that he's a long lost Cassadine heir. In fact, the first born to the first born. Of course, at their wedding, the recast Spencer finally arrives in town, about to find out he's no longer the Cassadine heir. And then that triangle that follows.
-Dillon returns to town to adapt one of PK Sinclair's novels about. Anna into a limited series or film, not knowing that PK Sinclair=Faison. (I'm not sure to what extent it was public knowledge, but I think it could be fun to have Port Charles go a bit Hollywood. (Yes, Skye can come back to town with him as a producer or something, and Lila Rae could come back with them.)
-Cody is not Mac and Dominque's child. Katherine is his mother, and the father is either Taub or Damian Smith. After her first tumble off the parapet in 1998, part of her deal when Helena saved her was that Helena would forge documents and DNA samples etc (this is a show that had an alien visit, okay?) so that her son (she gave birth before arriving to con Scott Baldwin and had him raised by whoever) would believe that he had a better mother than her. Of course, Mac is devastated to lose a son, but there is a woman he knew in Australia who coincidentally is at the hospital in need of a patient advocate with a private investigator background...who never told Mac that his last night with her before he left Australia, they conceived a child (and this would lead to Felicia tracking down this child, not knowing it's Mac's.) This would still leave Mac with a bio kid while not having that bio kid be Cody.
Also--Tommy Hardy comes back to reclaim his grandfather's legacy at GH.