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Unchecking a mod may not be simple. For example, some mods such as Convenient Horses requires entering stopquest CH to shut itself down before uninstalling or upgrading. Same thing with Vinis Food and Rest, or UFO.
Mods that use scripting do often run hidden quests to act as a programmable subroutine or hold global variables, but without proper deactivation these scripts will remain running within a gamesave even after the mod is removed.
It's always best to check the documentation/manual/FAQ that came with the mod to check for any possible uninstallation procedures, but unfortunately some mods have poorly written documentation.
As NMM generates and stores a custom uninstallation routine should a mod does not have it, the program will try to uninstall the mod using that routine, but it cannot "uninstall" the mod from a gamesave.
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