I just restarted NV the other day as I said I would earlier in the thread. So! Very different from 3. First off I noticed that I have to be WAYYYYY more careful how I pick perks, this is a good thing as it makes me pause and think about my character and play style. I tend to speak little and shoot a lot. The perks themselves always have a trade off, again making me think.
I choose to not follow the suggested storyline, but did travel the suggested route to get to New Vegas and made it safely. My PC helped the folks of Goodsprings since they helped him, then decided he would go work for the Crimson Caravan since being a Courier didn't work out so hot. After a few small jobs for them, and not being able to convince Cass to sell, PC went back to NV and to Fort McCarran to check out the Vault 22 since it was the only job offered.
Once he did that he had plenty of caps so he headed into the Strip where he meets Mr House and learns a few things. He then decides that if Benny is around, it might be a good time to go and deal with him.
Now gameplay wise I find NV harder to play, and 3 is easy, almost too easy. I would like it if NV were a little easier as I just am not a very talented gamer. So I am hoping for something in between the two as far as that goes, but better storyline like NV and the freedom that allows me as a role-player.