I think we should ditch Issac. They really screwed the story up in 3 (even though I feel like I was in the minority of those who actually liked 3, still the DLC screwed it). If Issac died at the end by pulling the moon into TV it would of wrapped it up in a nice closed trilogy.
As for everyone complaining about how 2 and 3 where less scary, well think about it. If you had to stop not one, but two marker uprisings almost entirely by yourself wouldn't you be a seasoned necromorph vet by the time the 3rd one came around? Issac developed as a charcter. He's not some clueless scared engineer anymore. I don't get why that was so hard to understand.
Dead Space 4 should focus on the aftermath of the unitologist destroying the Marker shroud on the Moon at the begining of Dead Space 3 and almost a sideline/continuation from the book, Liberation. Follow a different character who is apart of Earth Gov's "Last Battalion" as they mentioned in passing in the game. Maybe make the character "special forces" so theres more solo time spent making it more isolated and lonely like the first DS and not too much NPC interaction. Various missions basically centered around the Last Battalion trying to protect the civilians from themselves (dementia, scuicidal, and homocidal thoughts), necromorphs, and the Unitologist. The game would end with either destorying the Marker or having been able to rebuild the shroud only to see the Necro Moons in the skyline around Earth.
This game to test the waters and see if the market is ready for another DS trilogy or even DS in general. It gives fans a different side of the same story much like Severed and Extraction and also leaves a buffer for a developement team to listen to the fans and continue with the actual story and find out what's next for Earth and the Necro Moons.
Forget Issac. I still want to believe he died a hero destroying the TV Moon.