I gotta say bringing back Damage Threshold was a great decision as their are times where I love it and times where I absolutely hate it.

IMHO -

* Minimal level scaling.
* Certain wildlife inhabits certain areas. No more random robots spawning all over the landscape for no apparent reason.
* Wildlife has young. Deathclaws have proper packs. Feels much more realistic
* hardcoe mode
* Weapon mods
* Loads of quests
* Faction reputation
* Choice of who to side with
* Companion quests
* Effort to make game world seem plausible. Westside inhabitants growing food among urban ruins, affluent Vegas surrounded by underclass, portrayal of trade networks
* People dominate highways, go off the road and it's dangerous wildlife - feels more realistic.
* Getting rid of my first infirmary/laboratory that made addiction/radiation no problem at all.
* Well drawn factions. NCR well meaning but corrupt and incompetent, Caesar's dialogue justifying his totalitarian approach really well written (like most of the dialogue) and gives you a reason, albeit twisted, to side with him (I think Lanius is a bit too 'evil bad guy', but really good decision not to have Caesar a kind of 'Bwahaha!' cliched evil dude. Great choice of voice actor).
* Good choices in voice actors.
* Campfire/survival stuff needs some work, but good design idea.
* Levelling too fast, but balanced somewhat by great decision to limit perks and skill points. Makes you think about your character a lot more as opposed to knowing you're going to end up maxing everything out anyway.
* DT
* More weapons!
* Special unarmed/melee attacks
* Definitive, proper, satisfying ending. I really hope people moaning about a story having an end (like that's some kind of weird idea) you're explicitly warned is about to happen doesn't lead us back in future to sacrificing a meaningful ending just so people can potter around a gameworld they've already done everything worth doing in. Let's face it, they'll be the first to moan if the next title has more restricted choices of ending with your choices having less impact, just so they can continue to play in a gameworld that makes some kind of sense.
*Others I can't think of right now

Overall, best think for me is the attention to creating a more plausible world.

Fallout+Obsidian+better engine+less bugs would = gaming nirvana