
Short version:
New Vegas at first glance is just another Fallout 3 with a different setting, Desert. But, there are some feats that really change it up. Mainly the survival aspect. Now, the game warns you about the HARDCORE mode, with it, you will need to handle hunger, thirst and sleep in addition to enemys stronger stats. Adding to that inconvenience is that everything –
including ammo – counts toward your weight limit. There are also
limitations on your ability to fast travel – if your character would
dehydrate by the end of the journey, you won’t be able to embark until
you’ve had some water. It’s more realistic and offers a degree of
difficulty that’s hard to find later in the game. This mode is THE WAY TO GO for the ultimate experience. A level cap at 50! The repair skill is awesome now, you can merge similiar items to make repairs, with perks to enhance it even more. Karma is gone but you have a reputation with different groups that automatically makes you enemies with the opposing faction that you choose to collaborate and help. And you can now have 2 companions, 1 robot/animal and 1 human/ghoul. Another new thing and somewhat a quite big portion of the game is the Gambling, not only in casinos but they have a new card game thats called CARAVAN, and it is a bit like blackjack but not quite. All the gambling makes it a bit easier to raise caps. If you enjoyed F3 and spent atleast 100+ gamehours you will certainly spend an equal amount in this one.
Introduction
Players take control of a character known as the Courier. While transporting a package across the Mojave Desert to the city of New Vegas, the Courier is ambushed, robbed of the package, shot in the head, and left for dead. After surviving, the Courier begins a journey to find their would-be killer and recover the package, makes friends and enemies among various factions, and ultimately becomes caught up in a conflict that determines who will control New Vegas and the Mojave Wasteland.
-Wikipedia
My Road in Fallout New Vegas Ultimate

The biggest noticable difference straight away is the desert. Now I had a bit of struggling with that setting. To me, it was sometimes heavy exploring the desert, that was a challenge for me. Im not used to that setting in no way, and I felt bored with it at first, but after a time I reconciled with it since it IS a post apocalyptic game in California. The game and its mechanics are pretty much the same as in F3, but here you have something called Hardcore setting, where eating and drinking is a real factor for survival. Like if you get thirsty you get notified, when you start to get real thirsty you start to get stat penalties like -1 Perception and -1 Agility wich will affect the early character in game real hard. Another new thing is the post boxes. With it you can send items around the map instead of carrying everything. Now the story is as usual in Fallout universe really great! I won’t reveal it because I’d rather have you experience it for yourself. I can honestly say there is a crazy amount of replay value in this one, although its true for every Fallout game this is by far even greater. Not only because of the DLC’s but some of the quests you’re on you kinda want to know what would happen if I did it in another way, what would happen? Another funny thing about this game is it’s references to Cowboys, there are some cool revolvers that are really powerful for instance. Some new mutants that really change it up a bit in terms of combat style, and the Deathclaw seems easier in New Vegas, it’s my feeling anyway, I have’nt confirmed it by checking stats and such, but I reckon that some would appreciate that change. Not me though, I like the challenge. My first run was on Hardcore but that’s just me. I have currently over 1000h playtime on PC, and somewhere around 400h on Xbox360, and I still feel that I could start a new char and still discover new things. Now, I don’t google things in games like these because I feel it ruins the experience of discovering stuff. I have friends that read guidebooks and they ALWAYS miss out on quirky funny stuff. It really does’nt matter HOW you play this game because it is beautifully made for anyone that enjoys a RPG (Role Playing Game). I made a Brute as my third character and it was crazy, I could beat with my hands 4 Deathclaws in a fight and still be like, yeah yeah whats next. The DLC’s are way harder, theyre big theyre almost like a whole new game with somewhat different settings but they are AWESOME aswell. Some of them have a level requirement to engage in and even then they are way harder then the main game. As always Fallout games have a Brahmin load of sidequests that enrich the Fallout world and its inhabitants in the same funny and dystopian way as always. Youll have great fun FOR YEARS TO COME with this game.
