Changes you'd have made

1. President Reynolds stays on as the main villain of the series. The Company could have still been a part of the plot, but not as much. They can just be people influencing her in the backgrounds like in season 1. They don't get the main focus of the show, and the General isn't the main villain.

2. The conspiracy stays focused on Lincoln's set up and the events and reasons surrounding it. Once the Company takes over the show, Lincoln's frame job and Terrence Steadman becomes barely an afterthought. I'd keep those issues at the forefront. No shadowy company running the world.

3. Cut the baggage in season 2. No C-Note and his dumb family nonsense. Such a boring storyline. He dies escaping or early in season 2. Bellick either commits suicide when he considers it, or stays locked in Fox River forever when he's framed by T-Bag. No shoehorning him in storylines that don't need him.

4. Stop constantly changing T-Bag's character. It's one thing to make him three dimensions, but the shift between good and evil, mainly in season 2, was idiotic. First he wants revenge on Michael, then he wants to stay on as the fake Cole persona, then he starts being good by telling Lincoln to spare Gretchen and sparing a Company agent's life, then he wants to rape Sara? Just dumb. Keep his original season 4 motivation, getting revenge on Michael.

5. No Christina Scofefield. No Scylla. As already said, Reynolds stays as the main villain. Have the final season be about bringing her down.

6. Change or remove season 3 entirely. Don't fake Sara's death. Just have her be unseen the whole season if the actress wasn't available. Or at least fake her death in an explosion or something if they had to. A fake head in a box is moronic. Lincoln seeing the building he thinks she's in blowing up is a little more believable.