Usually a big mod problem. Sometimes depending on the type of mods you use, they conflict with each other and cause a CTD. you just have to experiment with the mods to see which one works, and which ones do not. Sometimes one mod does not work with another mod, and has nothing to do with the game, and it crashes.
The best advice I have... find your favorite mod configuration and leave it. Never change it unless you really need to. I have several copies of the game on my laptop, with different configurations just to change it up.
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