You can do serious damage in the registry, but if you just search for Silent Hunter entries then you'll be fine.
After all, the registry is only a list of items on your PC so that windows can keep track of everything.
For example, you can intall SH3 on a 2nd HDD, with no operating system and no registry entries will be written until the first time you run SH3. It only tracks the location of your files.
As for the Res Fix, I don't use it & as such am unsure how you might totally remove it. I'm sure someone here will be able to help there.
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