There's very little at this point that hasn't been subjected to mod of one kind or another within the realm of Skyrim - but one total conversion, Ultimate Skyrim, aims to overhaul the entire game, and has just released it's version 4.0 update which brings a lot of new features and enhancements.
It's not exactly a mod in it's own right - it's a massive modpack for Skyrim that aims to totally convert the game into an "unforgiving landscape, where only the strong and clever survive."
There's little that the combined mudpack does not touch, though, with completely overhauled combat, progression, the factions and economy, and of course, the game's visuals. It adds brand new areas, all-new enemies, items, and more.
There's some good news for newcomers, too - while previous versions required you to be a patreon backer to get the auto installer, the new version 4 release has done away with this and made the autoinstaller available for free - so it's pretty easy to install.
You can find out more and get the autoinstaller from the project's website, here.