From Before I Play
- Charisma is fairly useless as Speech checks are far more frequent in dialogue than Charisma checks and you can simply tag Speech if you want to be good at talking.
- While Luck is otherwise not crucial, the powerful "Better Criticals" perk (+50% critical damage) does require 6 Luck and 6 Perception.
- Intelligence is useful on any character as skill points are valuable no matter the build.
- Tag whatever skills you believe to be useful at the start, safe choices include at least one weapon skill and Lockpicking/Science. You have the chance to readjust your character build after finishing the tutorial.
- Hacking and lockpicking always require either 25, 50, 75 or 100 Science/Lockpicking, so aim for those thresholds. Lockpicking is arguably more useful of the two as many things accessible by hacking can also be broken into with lockpicking.
- The Repair skill is very useful, though you will eventually encounter NPCs who can repair anything to 100% if you can afford it. Also, unique weapons can also be repaired with their mundane counterparts and vice versa.
- The perks providing extra skills points upon level ups (Educated) and from books (Comprehension) are both worth taking early. Other skill point (and experience) increasing perks tend to be skippable.
- While Bloody Mess can be funny, everything exploding into chunks can make looting enemy groups a chore.
- Don't forget about Intense Training if you're having trouble picking a perk.
- It's worth picking up as much as you can carry from the starting area for some early spending money and repair fodder.
- It's possible to skip parts of the main quest if you're enthusiastic in your exploring, but it won't break anything.
- Holding down the Pip-Boy button activates a short-range flashlight.
- When hacking, you can always back out and retry mid-attempt to avoid getting locked out. Also, finding closed brackets like () or  in the garbage between words will remove wrong answers or refresh attempts.
- Handling the atomic bomb situation in Megaton nets you your personal housing where you can safely stash your gear and rest.
- Certain miscellaneous items such as Pre-War Books and Sugar Bombs can be given to specific people for extra money. Nuka-Cola Quantum bottles are of special note as 30 are required for a certain quest.
- Keep an eye out for Vault-Tec bobbleheads, one exists for each skill and attribute and give permanent bonuses. One (Medicine) can be found at the very beginning of the game on your father's desk.
- Ammo and stimpaks have no carry weight so they essentially double as currency. If a vendor is out of money, consider trading your loot for ammo and stimpaks which you can later sell to someone else.
- While headshots tend to be the most effective in combat, sometimes it can be worth crippling an opponent's arm to disarm them or their legs to reduce their movement speed.