I'd like to see Geneforge 5 take place in a post-apocolyptic setting. The Rebels win in Geneforge 4, unleashing the unbound. The Shapers respond with their own unstopable, ruinous creation. By the time Geneforge 5 starts, most major cities have been reduced to ruin and people (along with intelligent creations) live in small enclaves, in constant fear that an unbound creation will stumble upon them. Rebels and Shapers no longer exist as organized bodies.
The PC could be an ex-Rebel, ex-Shaper, or maybe just someone who stumbles upon a Geneforge. The goal of the game, at least initially, would be one of survival. Think Fallout.
I think that setting would make for one awesome game.