I have not run into this sort of issue YET with Skyrim, but I do recall that many other games can run into this issue when the total number of open files becomes too large. You mention a large number of mods installed, and I would be willing to bet that each or at least many of them, are using exported textures/nifs etc, as individual files instead of being packed into a .BSA or other archived format. Likely, if you pay close attention to "when" the error(s) show up, it will be related to total length of time that the game has been open and running and that the total number of open files will be higher. WHen you next run into the issue, save, quit to desktop, and restart from that save, see if the issue is still there or not. If not, then it is related to open files in some fashion. (don't get going on technical aspects of what OS etc, Guys/Gals, I have been providing tech support on PC's since the day when a PC was limited to 256k of ram. Despite what Microsloth claims, total number of files open issues have persisted and will continue to be an issue, extra ram only goes sooo far. quad core with 64 gig ram can STILL run into the same sort of issue. As it is not only the OS that handles/intercepts file calls, but the game and db engines used as well.)