Reason I'm asking is that I've read that some ini settings are saved with the save game (FOV for example), and that we should make a backup before doing ini edits. I have some questions around that:

1. Why do they include these settings in the save file when they are in the ini? Bad design choice?
2. Why do they endorse the ini tweaks from the tweak guide when this could potentially ruin a save countless hours in? (Or can it?)
3. Is there any tool available that can be used to edit a save game to reset any parameters to default values?

I guess I'm just a bit confused about what causes the CTDs I've been getting lately. I did some recommended ini tweaks from the tweak guide. The values I used were quite conservative. I also use SkyUI. These are the only mods I use and my game worked flawlessly for many many hours.

So if those tweaks were unstable then why didn't I have crashes before? I find no logic in the arguments that those tweaks should have anything to do with the crashes. For me it's clearly connected with the amount of hours played.

Please give me your thoughts and correct me if I'm wrong about anything (or everything ) of the above.

The only tweak that I know can cause problems (in terms of saves) is ugrids, and there's a lot of information available about why it's "dangerous" and how to back out if you need to change back to the default setting.

In terms of why it's causing crashes--I don't know, largely because you haven't provided any information about your hardware or the ini changes that you made. I've played over 400 hours, and my ini has been significantly tweaked for almost the entire time. But I'm also familiar with past games.

A simple test is to backup your ini files (Skyrim.ini & SkyrimPrefs.ini), then delete them, and let the game rebuild them. Try playing for a little while, and see if you're getting crashes. If not, then you know you did something wrong. If so, then it wasn't the ini changes that are causing the problem (and you can revert to your backups).

In case I wasn't clear above, ini changes (except for ugrid, and there are ways around that), won't mess up your saves.

Ok, thanks for clearing that up.
My rig:
Intel i7 - 860 CPU
ASUS P7P55D-Deluxe mainboard
4GB OCZ 1333 RAM
Win 7 64-bit
Radeon HD 5970 wth 12.2 preview drivers

I didn't do any ugrid tweaks, just some conservative shadow edits and fov. And also I used SkyUI.

But, yesterday I joined the beta and for that I went completely vanilla (apart from fov tweak in ini). And now I have played for many hours without a crash. So maybe the beta fixed it. I sure hope SkyUI didn't cause the crashes, because I love that mod.

BTW, the only crashes I had was on loading screens when loading a new area. Sometimes it just hung there playing music.