What if in G5, Spike became a recluse?
Then it’s revealed that Twilight started Twilighting when racial tensions started to come back, and her solutions only made things worse. Spike, seeing how bad things were, decides to resign as Royal Advisor and second in command. Twilight, in her anxiety, accuses Spike of treason and declares him an enemy of the state, forcing Spike to go on the run and flee to the far reaches of Equestria.
Sometime after, Twilight dies, and Spike was never able to make amends with her.
Or would that be too sad?