1. The main quest is fairly short, so enjoy your time in the wasteland - do quests as you come across them.
2. Survival is not an essential skill, i was never once short on food or water - even when i tried to be.
3. hardcoe mode is not so bad, but put some effort into being an effective shot for bigger battles (maybe invest in some VATS type perks)
4. Limbs do cripple a lot, this is especially true late in the game...so maybe stock pile doctor's bags or invest a spot in adamantium skeleton...because you can't aim with a broken arm or flee with a broken leg.
5. Do not take followers into casinos, sometimes you end up with their unique weapon and can NOT give it back.
6. No one sells a lot of any good ammo (only 9mm and 10mm) learn how to use a reloading bench.
7. Use a weapon you like, you really can't go wrong - don't focus too much on finding the most powerful gun, etc...
8. Beat the main quest on hardcoe mode so that you can play again and selectively turn it off...explanation below.
- I love hardcoe mode, don't get me wrong...but here is the problem i encountered. I enjoy making the game as realistic as possible, so the food thing is really cool. The problem lies with crippled limbs - I ran across just a few doctors bags (and yes you can craft them, but i didn't see hardly any forceps). There are also only a few doctors in the wasteland, so you have to travel a long way to get a limb healed. It's not that i minded walking, but sometimes it severely gimps your ability to stay alive. I wish that with a high enough medical skill you could have been able to repair limbs to semi-working order so you can fight and then find a doctor. SO i suggest switching off hardcoe mode to repair limbs and then turning it back on again. I know this sounds silly and "o, your taking away the realism" but honestly if you die you can't come back to life in REALITY, so better to pretend i'm a competent medical practitioner then to die because my leg got smashed with a slab of concrete. All that being said I plan to take adamantium skeleton this go around and see if it makes a difference.
---So, those are just a few tips i would have liked to have seen before i started through, so i didn't have to reload old saves. I am sure there are more out there so feel free to add or comment. One additional note, if anyone is on the fence about this game. It is really amazing, sure it has its flaws but they are far surpassed by its shear enjoyment - I was so disappointed it was over, but still knew i wanted to play over and over again due to the exploration of factions and stellar writing. Is it as good as Fallout 3? well probably not just yet, but with a few expansions it will be in the same sentence. And as for the bugs, i only encountered one or two freezes, but that was usually due to playing for several hours straight - what do ya expect.