If I had to guess I'd say that Ellie and Joel will both return for the sequel, it only makes sense from a marketing standpoint. Sure TLOU is a complete story, and doesn't really need a sequel, but the success of the game points to franchise potential - and the original game + Left behind paints Ellie as strong protagonist to carry the franchise forward.
If I was writing it I would have the player start off in Tommy's town a few years later, probably open with something like the deleted scene shown during the one night live presentation. You control Joel and sure enough something goes wrong with Tommy's town's defenses and all hell breaks loose. You fight hard alongside Ellie and Tommy but eventually the town is overrun and you have to flee.
I would also write in a potential love interest for Ellie that makes it out with you, just so you could have some over-protective father drama with Joel. This, in addition to the lie told at the end of the first game, makes Joel and Ellie's relationship uneasy through most of the early game.
At some point the three of them get ambushed by infected, Ellie and the love interest get into a no-win situation and Joel gets bitten while rescuing them. Joel asks Ellie to end it for him, but she refuses. At this point Joel reveals the truth about what happened in Salt Lake City, hoping it will convince her to kill him. Instead she leaves him to die alone.
She decides to head back to Salt Lake City to try and find any remnants of the Fireflies, hoping to eventually sacrifice herself for the cure. When they get there, the love interest figures out her intentions and tries to convince her not to do it. Resolute, she decides it's best to part ways and go it alone.
She gets a clue from Salt Lake City that points her in the direction of another potential research base. Along the way she encounters a few different scenarios where people are in dire situations is able to rescue them, becoming a hero to some.
In the end she gets there and of course, something happens that prevents the procedure from being done. Say some band of assholes come along to raid the site - killing many, while abducting women or children (maybe for meat like David's bunch). Alone and unable to fulfill her purpose, Ellie contemplates ending her own life.
Before she can, one of the survivors finds her and asks for her help to rescue the some of the abducted. Ellie agrees, and eventually succeeds, and in doing so realizes that she has found a reason for survival: helping others. With the skills she has acquired, in addition to her immunity to the bacteria, she becomes a warrior for people in the land of the dead