Huge difference
Edit: Sorry, a bit late.
I actually prefer the vanilla... 
But yes, mods allows the player to customize the game to their personal taste. More options is always good.
Like Xety, I dont usually mod a game unless it is really annoying the hell out of me - I much prefer a vanilla experience whenever I can. DAO.... I had to mod the female body. I cant stand the gorilla posture. I tried, tried very hard but sorry devs... it is too much.
As for FO4, I am like the Sanctuary settler Long. 80% and rising happiness but I just have to whine about the 20%. Mainly because I believe Bethesda could have done better. Will mods be able to save the conversation? I dont think so but only time will tell. After near 200 hours, I have all but given up on the story. Conversation wheel aside, 99% of the "options" does not make a difference. Tis basically at most 3 options - yes, no and later. More than half the time, it is either yes or later.
Generally... (not all - dont tell me there are cases that the following does not apply because there are more of the following than exception to the following. Much more):
NPC: You help me yes?
PC: (Ok) - help him.
PC: You Nuts?
NPC: Yeah I am nuts. Now lets do this!
PC: 
PC: Tell me more?
NPC: In due time my friend. Now lets do this!
PC: 
PC: NO
NPC: I will wait here. Come back when you pick one of the above.
PC: 
Now, how can I be playing and enjoying myself for like 200 hours without giving a darn about the story? Because the game itself is truly very enjoyable; maybe because I like to shoot things, chop things and shoot more things and find new places to loot and build. Ah.. and hunting legendary - it is Borderlands all over again 
FO4, even without a story, is an extremely enjoyable game. A sandbox world that you can just go and do what you want without the weight of a plot on your shoulder. Unless... you hate shooter for some reason... but sniping the heads off a bunch of super mutants and feral ghouls as they charge towards you and finishing them off in melee with a huge hammer in VATS mode - EPIC. Never gets old. 
p/s: My headcanon - I am a Space Marine Terminator - I wield the mighty Storm Hammer, Plasma Pistol and Heavy Bolter in Power Terminator Armor. I will cleanse this world in the name of the Emperor! The stupid child is just chaos gods playing tricks on me. Good one but I aint falling for that. (Only found red paint... so I cant be UltraMarine... ah well, Blood Raven it is
)