How cool would a Secret Invasion/Nick Fury Vs SHIELD type story be? Maybe Coulson finds out that the Skrulls are infiltrating SHIELD (and other powerful organizations) and A) takes a "Trust No One" attitude, goes out on his own and his team has to track him down... or B) Coulson takes his crew out on their own while they try to figure out what's going on, who they can trust and how to detect them, while on the run from the rest of SHIELD.
Either way, SHIELD and Victoria Hand are NOT happy.
Paranoia is rampant, Coulson and/or Ward picks up a Jack Bauer-like attitude, we find out that one of the crew was replaced at some point OR was always a Skrull... it could be fun...
If they can get the actress that plays Hill when How I met ends, I'd love to see a Hill vs Hand subplot that has Hand trying to undermine Hill's leadership role.