To add to Talonfire's difference list:
There's also the matter of the followers. (I've never done FO1, methinks now is the right time).
In FO2 the count of followers you could get at the same time depended on CHA. And there's a perk - "Magnetic Personality" which allows one to acquire one more follower. You could get a decent squad of 5(6).
Possible followers include:
A tribal who wears a bone of his grandfather as a makeshift moustache;
A fat trader calling you "Boss";
A bartender... who's wicked with the Gauss rifle (small guns);
Ladies and gentlemen, the man who invented Jet himself! Myron, baby, Myron!
A ghoul doctor.
A supermutant sheriff who's nothing like Fawkes - both in manners, and, in intelligence.
A supercomputer downloaded onto a bot (req you to get a brain; depending on your SCI skill, you get a brain, and the bot's abilities depend on the brain. So much for hacking computers as being the only thing SCI is good for...). The AI's called Skynet.
An intelligent talking deathclaw.
A Dog, and a few (two?) robot dogs.
Oh... and a spouse/husband due to a shotgun marriage. Better keep those pants on outside of New Reno
Also, there's the thing with the car. Now, the car's not something you roll on constantly;
Think of it as of something of a mobile storage that appears on the map where you appear. And makes fast travel faster. It requires to be refuelled from time to time. And, can be stolen in New Reno.
Also, random encounters. You get those only whilst fast travelling; You just get "dropped" into an event. And, the event might be also a battle - not just "something cool happens". Nasty if you're low on health.
Power Armor. Now, be very very wary of any type of PA, especially the Enclave's one (advanced power armor mk 2). BoS is scared of it in FO3 because of the one in FO2. You don't want to mess with the ones wearing it. Pistols and rifles? You need a critical from point-blank to the eyes to score any reasonable damage. Big guns, energy, gauss. Sniper rifle/caseless SMG/.233 pistol/assault rifle in worst-case scenario. Nothing less for a single enclaver.