Play it first with no mods, then maybe add some lighting mods or high res textures if you don't like the look of it after a few hours. You should play the game as it is first though, but that may take you a long time. I've spent nearly 200 hours on it minus mods or DLC. You could easily enjoy it without any game changing mods. I'd say try to go through the main quest (and a few others) without mods and then maybe go mad with it...
Only reason to add mods is when you stop having fun with the 'vanilla' version.