What issues make you too scared to play with the main save?

If the game have more toggle on-off of things I want to disable, I would have to get many mods. At least, Neighborhood Stories can be turned off completely.

Your choice for not using mod is the safer way to play. You can update the patch without too much worry like heavy mod players. I'm in the middle of them, just want to make sure I understand what affects will be added each tine.