dialogue system:
I like the idea of it, being more cinematic. The old games had this static time-freezing dialogue system that was pretty immersion breaking.
The dialogues itself could have a bit more depths to them. I'd like to have more than 4 options.
karma and skill system:
Both were pretty outdated in Fallout 3 and NV... I liked the skill system in Skyrim way more and actually really enjoy the one in F4.
Perks finally have some depth and started to matter.
I'd love to have something else instead of the Karma system, that lets you play an 'evil' character, but the Karma system barely ever had an impact in the old games... so that's something that all games did wrong.
quest design:
So far it's been good, being 40+ hours into the game. It mainly helps you discover new places and explore the world, explore the stories of the people that had to live since the bombs fell.
I didn't really care about the main quest though, so far ^^ Why would I want to search for my son, if I don't even know how many years have past... and seeing how dangerous and deadly the world has become.
I play like my character already gave up on him 
rides / cars:
I really hated the way horses worked in Skyrim and Witcher
they make you skip so much of the world and just feel weird.
game engine:
It's impressive. The graphics look great. The actual engine itself feels impressive.
You have hundreds of locations. Let's say you go into a house and see an empty milk bottle on the table.
You accidentally make the bottle fall over and leave the house.
You visit the same house 50+ hours later and see the same milk bottle, still lying there fallen over...
It's beyond me how hard it is, to make an engine like this... to make the game actually notice, what you have done in the world and save every small thing.
There isn't any other game that is able to do this... most other open world games, just have a static world... Fallout does not
And I have yet to see a bug, where someone clipps through walls or falls through the floor.
companion AI:
I never used companions in any Fallout or Elder Scrolls game... it feels like cheating ^^ they are all so strong, can carry way too much and always mess up your sneaking 
I love the new 'Lone Wanderer' perk, that gives me an advantage for not using companions <3