I'd say it's not as story driven as NV. There's more open world to explore in FO3.
I would recommend doing the Main Quest for the first time, although you can still do lots alongside that of course.
Keep in mind that without the Broken Steel DLC, the game ends when you finish the MQ.
(Broken Steel extends the MQ and lets you continue playing after)
There's no reload/crafting tables. No weapon mods either, but you can build more weapons from raw material and they are great (Railway Rifle FTW)
It's easier to become really powerful in FO3, NV made it much tougher to survive. (skill books everywhere but no magazines in FO3)
The skills are basically the same, except you'll see there's
Big Guns and
Small Guns, (and Energy Weapons.) No Survival skill, no hardcoe mode.
The world feels more crowded and full of encounters. A lot more "dungeons" to clear out and mini quests to find.
There's Bobbelheads to find hidden in the world which improve stats, instead of buying implants.
Charisma is even more useless in FO3.
Weapons and Armor have less stats to worry about. And there's only one type of ammo for each weapon. (no armor piercing rounds, etc)
The complex relationships between the Factions in NV does not exist here. No need to wear disguises. Not really any politics.
Karma plays a bit more of a role in how people treat you, but still barely a thing to worry about.
No "iron sight" on guns.
I've rambled on enough...
there's more, but that should point out some of the big differences.
Overall, I think I like NV a little bit more. But FO3 has more atmosphere and interesting places/people to discover.