The biggest downsides are that you have to restore the original Data folder which means probably reinstalling Skyrim, although you could probably do it by deleting everything but the bsas and esps of skyrim and its official dlc and having steam check the files. It's got a nice feature where you can hover your mouse over a saved game to see if it's missing any mod files, and if so, MO gives the option to automatically enable all the mods that save is missing. The profiles system allows for profile specific mod lists, as well as INIs and saves. But I like the system MO uses where mod files never interact with one another and the original data folder is never altered unless you use something that MUST alter it directly (such as SKSE).
Since I started using it almost 6 months ago, I've never regretted it. It has a fully fleshed out profile system.
