What if Penny grew up with Sheldon in East Texas? She could be friends with Missy, but she sees some of the neighbor kids picking on Sheldon when he decides to build his Death Day, and so she beats them up and they become really good friends. They talk all the time as they grow up, and when Seldon is done with school and gets a job in California, she moves out there with him to pursue her dreams of acting while still living with her best friend. And when some of the guys from the University start picking on Sheldon (Leonard, Howard, Kripke, hell even Wheaton), she marches right up to them and puts an end to it.
Long story short, Penny and Sheldon vs the world. Gen or romantic is completely up to the filler. I just love Penny defending Sheldon, and Sheldon taking care of Penny in return.