do you start the game with the SKSE loader, and if so are you sure that's up to date? SkyUI requires it so you may already have it, but not the version compatible with the newest update. (?) anything else that might not be controlled by NMM, like Scriptdragon or the TES accelerator? Does it just crash to your desktop when you try to save on a new vanilla game? How many save game files do you have? if possible you could try cleaning out some of the old ones. You could also try a complete sweep. save your necessary saves to a backup folder somewhere, then delete the folder. delete the folder that has your ini settings (i think it's documents/my games/skyrim) then through steam delete the local content for skyrim. do into steamapps/skyrim and delete any remaining files then try reinstalling through steam from scratch, don't download anything additional, even the texture dlc. start a new game and see if you can save. if so start 1 by one to bring the mods you had back in. hopefully some of this will help