Have you deleted the Save folder? By default, that would be "C:\Users \Username \Documents \SH4". The game actually pulls a lot of its data from that folder to run. After deleting the Save folder, can you run the game? Are you able to run a "Quick" or Single Mission? Did you install the DirectX v9.0c and Windows Media files when you installed the game?
If you can't get going after clearing the Save folder, then I would recommend de-activating all of your mods, and trying the Stock game by itself, and see if it will allow you to Save. If you get operational, add the mods back in one at a time and test again. If you're still no-go after de-activating the mods, then a re-install of the game, and trying stock would be in order = after you clear that Save folder again.
Now that I think about it, where are you when you're trying to Save the game? Are you in the office, or on the boat? Can you Save from a Single Mission?
