Fallout: New Vegas
- Lockpick, science, and medical are excellent all-purpose skills. Survival and barter are a waste of skill points (Although note that if you want to play a diplomatic character, Barter and Speech are used a lot in dialogue).
- Take the educated perk at level 4 for lots more skill points (52 by the time you hit level 30).
- Your Strength, Endurance, and Intelligence should not be too low, and your Charisma should not be too high. Don't put points in Survival. Beyond that, there is literally no way to fuck up your character. Do whatever feels right. I should mention, though, some perks are not very good. Anything that deals with experience, radiation, or dialogue options isn't worth it.
- Speech is amazing in Vegas and has the most conversation options associated with it. Repair is also a pretty solid choice, and I would advise at least getting it to 50 for weapon repair kits.
- All of the weapon skills are viable from my experience, though unarmed might be the easiest.
- Pick a combat style and go all in. Whether it's Melee, Unarmed, Guns, Energy Weapons, or Explosives, pick one, and pick out perks that support it and work well with it. It doesn't hurt to be putting points into a secondary weapon type, but focus your combat perks on whatever you intend to be best at.
- If you go Unarmed, don't neglect Melee as a skill, it's required for some key perks (and vice versa).
- Oh, and if you start with 7 Luck you'll be able to basically ignore money from about 1/3rd of the way into the game onwards. Just play Blackjack. Lots and lots of Blackjack.
- I recommend taking the "Wild Wasteland" perk... It's needed for the Alien Blaster. If not taken, in place of the Alien Blaster will be a unique Gauss Rile. While its a nice weapon in of itself, I preferred the Alien Blaster.
- You'll only get 100-150 rounds of Alien Blaster ammo all at once, and never again. Despite that don't be afraid to use it...that's more than enough to take out most of the really tough enemies like Deathclaws and bosses.
- The Plasma Caster is probably the best all-round energy weapon in terms of damage, fire rate and ammo usage. Get to New Vegas ASAP and head to the Silver Rush to find it. However it can't be purchased so you'll need to steal it or just kill everyone in the Silver Rush. (They're assholes anyway)
- Having trouble with them goddman killer robots? The Pulse Pistol is a unique weapon that'll make every single robot fight laughably easy. Find it in Vault 34.
- The Meltdown Perk causes enemies killed an energy weapon to explode in a green corona and inflict damage to nearby enemies...who in turn will also explode should they be killed, causing a chain reaction of explodiness. Seems gimmicky at first but its actually pretty devastating if you use high-damage weapons...particularly the Alien Blaster. In some indoor areas you'll be able to kill five or six tough enemies in one shot. (which has the nice side effect of conserving ammo) The downside is that Meltdown is also really good at killing melee-oriented companions since they always get caught in the corona...you'll need to stick with range-oriented companions like Boon.
- It's a good idea to invest in the Science skill as it will allow you to make the Overcharged and Maximum charged energy cells. You'll inflict greater damage at the cost of faster weapons degrading, but you can offset that a bit by investing in Repair so you can make repair kits and taking the Jury Rigged perk.
- Don't bother taking the Laser Commander perk...by the time you're high enough level to get it you'll be using plasma weapons exclusively and most late-game enemies shrug off lasers.
- In contrast to every earlier Fallout game, flamethrowers are now considered Energy Weapons.
- Choose one weapon skill to specialize in to start. Explosives, unarmed, and energy weapons are all tougher but doable to start with, guns or melee weapons is probably better for a first time.
- Speech skill matters. Survival and barter don't.
- Don't take the perk that increases your XP gain, you'll hit the level cap even without it.
- If you piss off the NCR early, the game will be a lot tougher, but maybe you'll want to piss them off for roleplaying reasons. There will be a point in the story where if you have negative reputation with either the NCR or the Legion, it will go away, so if you regret pissing either side off, stick with it and you'll get it reset.
- Get companions and the combat will be easier.
- Run from Cazadores until you get lots of poison antidotes or have done the Old World Blues DLC.
- There is no way to totally fail most quests (except contradictory ones from different people - kill this guy vs rescue this guy) so pick a character archetype to roleplay and just do it. You might "fail" some quests but you really won't.
- You don't have to rush to New Vegas but it's pretty cool so don't dawdle too much.
- Play through the DLC in release order, so Dead Money, Honest Hearts, Old World Blues and then Lonesome Road. They're individual side stories but each one also contains buildup for the last one and they're all pretty awesome in their own ways. Dead Money recommends level 20 or higher but I've done it at level 10 and didn't find it hard, other people absolutely hated it though so your mileage may vary. It does have some quite high speech checks and lockpicking doors so maybe get those skills up before going in if that stuff is important to you.
Repair
On the note of repair. It may be, depending on your play style, worth it to boost it to 85 to take the perk which lets you repair weapons and armor with anything considered "similar" to it. This means repairing vault armor with vault suits of cloth or power armor with anything vaguely metallic.
Works on weapons too obviously, letting you repair rare weapon types with much more common and often purchasable weapons. And since you'll have a minimum of 85 repair you'll be getting damage bonuses and everything lasts longer.
Granted if you're going to jack up endurance and strength, this doesn't apply so much.