Without giving ANY spoilers, I am going to start playing NV since I kind of know to much of the story, places of FO:3, and now it's boring.
So what should I know about NV -- without giving spoilers, and since i'm on this topic, what mod's are highly suggested (nothing game changing, not til a second playthrough).

Well nothing, just go in and play. It's not like you'll die every minute because you don't know the secret to new vegas. I think you'll enjoy it even more if you just knew nothing about it.

Default night sky looks like brahmin doodoo (same star texture as FO3) so I changed that.

Added a new moon texture to go with above.

Default nights are way, way, way too bright. Fixed that.

Default binocs has the moronic cartoon shape and poor magnification. Fixed.

Hit level 30 with less than 1/2 the game completed. Had to start a new playthrough, this time with an XP suppressor.

(Personally detest the 1perk/2levels so I fixed that too.)

Other than that it's all good.

One more thing: NEW VEGAS can become near-unplayable around level 6-7 through a combo of vicious enemies, low cap, and no loot. Grab everything not tied down and don't wander too far afield until about level 10.

Good luck!

same as he i hit 30 early on the main quest, hahahhahah , was all my foult bc evry time i see something cool on the screen i go explore it so yeah i get alot of Exp i shouldnt till late on the main quest =P but is a exelent game.... at least on PC since the patch and some mods and get myself i not have any major bug that dont let me enjoy the game, just the rando stuck body on the ground and after some sec you see flying 20fts on the air but is fun and dont make my game time bad.

Everything you should know now is nothing you would want to know later. Empty your glass and fill your head with the wisdom of the Mojave....

Don't go North to New Vegas first.

I don't think that's a spoiler. See you in the Mojave.

Explore..

That is all.

Save early and often, until you figure out where's not a good place to head to at low level. Staying on the roads is pretty safe, (well as safe as you can be), at lower levels. Do Sunny Smile's tutor mini quest, you get a pretty good beginers weapon and some caps out of it.

Theres nothing like just jumping head first into a new story without know the world your getting into. With that said the only thing you should know is the mods you should get from the start.

1. Fellout
2. Lings
3. Type3 (from Fallout 3 not converting needed when it comes to these) and breeze body replacers
4. Any mod you can find to improve textures (NMC is working on his texture pack for New Vegas right now, also a lot of the textures he did for FO3 will work)
5 Ok now this one is so important I will post the link for you. http://www.newvegasnexus.com/downloads/file.php?id=34778 for Nvidia graphics cards or http://www.newvegasnexus.com/downloads/file.php?id=34970 for ATI
6. ENJOY THE GAME :foodndrink:

If I can remember anymore I'll post them for you but these are like a must have!

Edit: oh and a lot of people have random crashes, I guess I was lucky and had non from the game itself but from random mods conflicting like beauty packs and lings. so you might wanna save a lot.

Save and save often? Also, don't complain if the game is buggy/glitchy/crashy.

If you decide to play on Casual mode, you don't have much to worry about. If you play on hardcoe mode, carry a few Doctor's Bags or Hydra and Fixer with you at all times.

Either way, carrying plenty of ammo couldn't hurt. For a first playthrough, investing in Guns is a good option. Also, remember to check mailboxes and magazine dispensers... Very helpful.

Make multiple saves (But you probably already know that from FO3 ) I see way to many posts about "Help I glitched and olny have one save am I screwed?" so hopefully this saved you some hurting down the road.

What you should know is that this is not Fallout 3. It's also not an expansion, nor a sequel.

Other important things:

Save. All. The. Time. In multiple slots. Do NOT rely on one save slot or the Auto Save.

hardcoe mode has *nothing* to do with difficulty.

Now go and enjoy it! The game is fan-freakin-tastic.

when playing for every 3 and a half steps your character makes , make a save . j/k save before every dialog with a named npc . save before going thru doors and before fast travel. And dont put all your trust into auto save.

You really don't want to do anything against a faction untill after visiting Vegas and leveling up, it's just not worth the headache imo.
Just explore a bit don't wander too far from any road, and expect a lot of creatures with high health levels.

Don't feed the Deathclaws.

Don't kill the coyotes. They'r sooo cute...

Remember strength requirement and the DT system.
High DAM = Good against high DT, High DPS = Good against low DT.

Always carry a shovel.

Yeah, I agree with some of the earlier posters. I've been playing the main quest for the past couple of days; Got about 10 hours of game play (with going to college, working two jobs, and hanging out with my girl friend and what not) and I'm already lvl 11. I remember playing Fallout 3 for the first time and it took me a good week to get to lvl 11 at least.

Keeps lots of seperate savegames - don't keep saving over the same single savegame.

Later in game, grab the Explorer perk.
I missed a LOT of places in my first playthrough.

Save often.

I really advice a rough learn curve playthrough.

hardcoe is the way to go to differentiate your experience from FO3 and Guns/Repair/Speech will come in handy on your first run.

VATS is less important (though with the right perks and weapons it could be made to shine again) and 1st Person shooting skills are much more relevant in NV.

sorry for the double post...