As with SH3, SH4 can be problematic with saves. I've ended 3-4 careers because I couldn't get back to port, no matter how many previous saves I attempted. At some point, the time compression would not work without slowing the computer at anything above 128. (I have a fast quad core system too.) When this buggy behavior occurred, it was almost inevitable that the game would crash in the near future, especially during screenshots. Many a time, I could not proceed beyond a certain latitude or longitude without a crash. Hopefully, you will fare better.
For my experience, SH3, though buggy with saves, was considerably more stable. In both cases, I try to follow the standard rules of not saving underwater or when ships are present, etc... Sharkbit is correct about the faster loading of saved games. It's a treat indeed.
I haven't actually tried the mods with SH4 yet, as I've been so busy with SH3 + GWX. I'm currently downloading TMO. Guess we'll see how that goes.
Good luck with your campaigns!