Advice for beginner...
1) Keep your Speech level high. Talk to everyone who has a name, and I do mean everyone. Pay close attention to dialogues. Information is EVERYTHING in this game.
2) Save VERY often. Diversify your saves, too. Between bugs, crashes, poor signposting and staggering surprises of the game's storylines, you might have to go back to an old save every once in a while.
3) Some followers have VERY strong feelings about factions they belong to, as well as factions they oppose. If they tell you they plan to shoot members of a certain faction whenever they meet them, they're NOT kidding, and it can get you into some serious trouble. Also, when traveling with a faction-allied follower, try not to kill anyone from that faction, for the same reasons.
4) For your first playthrough, go with Guns for a combat skill. You can try Energy, Explosives, Unarmed or Melee in later playthroughs, but it's best to keep things simple while you're familiarizing yourself with the gameplay.
5) Until you learn which items do or do not have uses, collect EVERYTHING. Hoarding is not a crime
6) Do not take the Wild Wasteland trait on first playthrough.
7) You get to respec once, just before you leave Goodsprings. That means you don't have to make your final choices of S.P.E.C.I.A.L and skills to tag right away. I usualy tag Explosives at the start to get some Dynamite and sell it for a bit of starting capital (Dynamite is the most expensive weapon you can receive at the start), then I respec to something else when I'm done doing all there is to do in Goodsprings.
8) Lead (as in ammunition component) has weight, despite the fact that your Pip-Boy doesn't show it. That weight can add up to serious values. If you've been converting different ammunition types at the Reloading Bench and you find some "invisible" weight on yourself, try unloading the lead.
9) Fallout Wiki is your friend. Even if you don't want spoilers, things like weapon stats and more intelligible explanations of perk effects will come in handy.
10) This forum and its people are also your friends. We don't bite. Ask away