How to play smarter, not harder. These tips will be relevant for almost any playing style, keep these things in mind for the entire game.
1. Save! I cannot overemphasize this enough. I suggest making a new save slot every time you enter or re-enter a city, and use one file to quicksave "F6" as you move around the city.
2. Loot: Play as a packrat, pick up every thing you see, search corpses and hidden nooks and crannies. Take things from people's bookcases, they usually don't mind. Your inventory will quickly fill up using this method, so use your NPC's as pack mules or liquidate some of your items for caps.
3. Put that gun away: Many towns do not take kindly to you waving a firearm around, if someone asks you to put away your weapon it's probably a good idea to take their advice. A good tactic is to put a weapon in your inactive item slot; you will appear unarmed, but can access your weapon without AP loss should a fight break out.
4. Try something new: Almost every problem in Fallout has multiple solutions. If you keep trying to snipe a group of super mutants and keep getting killed, try a different tactic. Try to rush and burst fire them, or attempt to sneak past and avoid the fight all together.
5. Drugs: Using chemicals is a mixed bag, drugs such as mentats, buffout, and psycho will give your character a temporary stat boost, and then drop your stats slightly below what they were originally, then return to their normal level. This process takes several hours. In addition to this there is the danger of addiction where your character will suffer severe penalties for not regularly taking his drug. If you become addicted it's a good idea to re-load immediately. I highly suggest using drugs when the going gets rough, buffout and psycho are great in combat for any character, and mentats will assist you in making conversation. See the Items section for information on the effects of drugs.
6. Watch the time: Remember your time limit. Don't feel rushed when moving around a town, time passes very slowly inside towns, take all the time you need. But when you travel around the world map the days get eaten up pretty quick. Your vault will die if you take too long to find the chip, so try to move efficiently around the world, move through deserts and cities to increase your speed. You are not the only person in this world; other forces are at work with their own agendas and you may find places destroyed if move too slowly. With that in mind, do not neglect to visit old haunts as well; things may have changed since your last visit.
7. Improve yourself: If you ever find a book or an NPC who offers to help you increase a certain skill, take it. You can spare a couple of hours to increase your skill level.
8. Talk to everyone: Most of the important characters are easily identified, but it's worth your time to chat with ordinary citizens. They are a great way to get the lowdown on the area you're in.
9. Cripple People: If you are having a lot of trouble with a certain fight, try an aimed shot. Go for broke and try to hit them in the head or the eyes, one lucky hit could win the fight.
10. Behind Walls: You can't see what is behind a wall unless your character moves right up against it, be sure to check everywhere though, the designers love hiding goodies where you can't see them.
11. Steal: If you are going to steal, do it diligently, steal from everyone you see, this is a great way to stockpile ammo and stimpacks.
12. The 1st Dialogue Tree: Most of the important characters, especially the talking heads, will have a unique dialogue tree the first time you speak to them. You may want to save and re-load to get the best first dialogue possible as you will not get another chance to.
13. The consequences: Your actions will have consequences. If you take too long in your quest, certain towns will be wiped out. If you threaten someone, they may refuse to talk to you again or even attack you. If you kill kids people will hire bounty hunters to take you out! Be aware of your actions.
14. When you open your inventory in combat you lose 4 AP's, but the number of actions you take inside your inventory window is irrelevant so do everything you can. Switch weapons if you need to, use a bunch of stimpacks or drugs, reload by dragging ammo into your gun.
15. Combat Messages: I like reading the descriptions of the damage you and your enemy inflict on each other, but it's oftentimes confusing whether or not someone was crippled, you may want to go to preferences and change combat messages to "brief" to avoid confusion during important battles.
16. Radiation: You will only encounter radiation a few times in your adventure and if you follow
the walkthrough you shouldn't have any real problems. If you use a geiger counter on yourself you
can determine your radiation level.
17. If you are having trouble duplicating something in the walkthrough, your character may not be smart or charismatic enough. Look carefully at the situation, if it involves bluffing someone out, your speech and charisma may not be high enough, if it involves a boxing competition you may need to become stronger and a better-unarmed fighter. If you are a girl you may not be able to flirt with someone's daughter, and if your karma is too low some people may not hail you as a hero. Remember, you can always pop a pill to temporarily increase your stats, or use items to increase your skill level. Every Fallout experience will be unique so not everything will work every time.