3DNPCs is well done. Regardless, just limit yourself to a handful of mods, for your first time playing.
This is probably, at the end of the day, the only content (quest) mod worth having. And I played them all, pretty much. Better written and more varied NPCs than the game itself.
To me, the SE vs original question is mostly one of mod usage. It's barely different, but there are mods that never made it over (and very few mods were made for it specificially, as far as I can tell.) In general, OG Skyrim will be for sure compatible with whatever you care to use.
I used every kind of mod for a long time, but I'm more of a minimalist at this point. I would get SkyUI, like everyone is saying. Here are a few others I wouldn't play without (alongside the aforementioned INPC):
Wet and Cold - it's just basic, no brainer, immersive stuff that doesn't have a drawback.
Jaxon Named Save - I like to know what the hell I was doing when I saved, not just what zone I was in
Enhanced Lights and FX - Most of the mods I still use are visual mods of some sort, and this is one of the most important; without it, interiors look very bland and contrast between light and dark is nonexistent
SMIM - another must have visual mod. It just makes a bunch of things look a hell of a lot better.
Alternate Start - not at first, but if you're like most people you'll start Skyrim a bunch of times, and this allows you to skip doing the (long) intro every time
Difficult Archery - never hear anybody mention this one, but such a small tweak makes so much difference… in the vanilla game, enemies will unerringly shoot you every time you peek over a rock. Doesn't matter if you peek for 1 second, or moved all over the place out of sight for 30 seconds beforehand, or if you're 200 feet away. Peek = thwack. This mod just adds some variance. Bonus: you'll hear arrows whiz past you when they miss.
Some kind of perk overhaul - the vanilla perks are boring. They really are. It might not bother you if you have nothing to compare it to, but once you use a perk mod, you'll probably never go back. My favorite was SkyRe, mentioned above, but I don't know how compatible it is these days. Perma was the "sequel" to it, but it never had quite all its bugs worked out and it has an ambitious, patch-filled install process. I think it's the most thematically cohesive and interesting one, though, so try it if you have some patience to read and follow instructions. Another option is Ordinator, and it's fine, but despite liking the author's mods in general (if you're a magic fan, use his other mods) I feel like Ordinator is a bunch of unconnected powers and doesn't really encourage builds like SkyRe/Perma.