I would like to see the Federation technologically out evolve or subsume the other Alpha/Beta powers (Romulans, Tzenkethi, Breen, Tholians etc) and expand out into the galaxy running across unusual new allies and enemies, It's already started to a small degree with the slipstream drive.
As for unseen events:
WWIII to Enterprise
Invention of Transporters
The Pegasus incedent (original)
Other races aftermath of the Desiny events, not just the Federation