Some of the lighting ENB's and texture mods can wreak havoc on performance like turok said. I ran into major headaches with my last videocard (560Ti) with the realistic lighting and darker nights mods, took me from around 70FPS down to around 20. When I tried to remove it the game would crash when entering dungeons. Had to reinstall the game or the mod to get it working right again, went with the former. I recommend using Nexus Mod Manager if you are not already, if you use a lot of mods (like I do).
You might try dropping the object & terrain distance and/or shadows if you don't want to use a resolution that is not native for your monitor.