Let's start with this:
Agent Phil Coulson pulls together an elite team of SHIELD field agents including Melinda May, GW Bridge, Clay Quartermain, Akela Amador and raw recruit Daisy Johnson, ably backed by scientists Leo Fitz and Jemma Simmons. They are tasked with tracking down people newly gifted with superhuman powers, rogue terrorist groups and alien artifacts, just as in the current show. However, instead of fighting "Centipede," they would encounter the remnants of A.I.M., who were regrouping under a new Scientist Supreme (George Tarleton) after the death of Aldrich Killian.
(Rule #1: No agent sets foot on the Bus who isn't an expert in weapons and hand-to-hand combat. That means that FitzSimmons would be secretly badass, like Coulson.)
That's mix of agent-types I was sure that we would see when the show was announced, very well-defined characters from the comic book universe along with some original ones (and of course Coulson). They could have all been original, as far as I'm concerned, but they should have had strongly delineated personalities from the start, along with their own personal agendas that would have created organic sources of conflict on the team. Bridge and Quartermain are hardened vets who would have problems with Coulson's unorthodox style. Amador chafes against authority and hates the team concept. Johnson is young and gifted but she makes rookie mistakes, so Coulson would mentor her. Definitely someone would be reporting back to the WSC and Alexander Pierce, setting up a tie-in to the Captain America movie.
Those are the basic changes I would make to the show's initial structure. Coulson leading a team of badasses into the field with brilliant scientists providing support is what I expected to see on screen. No untrained assets, no floundering on missions. Just serious, expert SHIELD agents.