This entirely depends on the character being played as. There's another topic on this board about the worst perks. Whatever isn't listed there is good for at least some people. Obviously though, a small guns character will find Pyromaniac or Iron Fist to be worthless perks, even though those are otherwise useful for other characters.
I'd avoid getting a perk that raises a skill only because you'll have plenty of skill points without it. (Like Little Leager, or Daddy's boy/girl)
Swift learner is also usless.
These are all the skills i think are worth looking at. I got rid of maybe about 1/3 of the ones on the list because their completly useless. go to this site to find out more about each one http://fallout.wikia.com/wiki/Fallout_3_perks
Action Boy (Girl) Adamantium Skeleton Animal Friend Better Criticals Bloody Mess Chem Resistant Chemist Child at Heart Commando Comprehension Concentrated Fire Contract Killer Cyborg Demolition Expert Educated Entomologist Fast Metabolism Finesse Fortune Finder Grim Reaper's Sprint Gunslinger Intense Training Lady Killer/Black Widow Lead Belly Lawbringer Life Giver Master Trader Mysterious Stranger Nerd Rage! Night Person Pyromaniac Rad Resistance Scrounger Sniper Strong Back Tag! Toughness
Just about to hit 20 and give Grim Reaper's Sprint a try. From what I hear, it's broken good. Supposed to be utterly sick. Just make sure you've got the AP to make effective use of it.
Demolition damage boosting one gets utterly ridiculous too. With all the schematics and high demo skill and those boosts, you're looking at absolutely absurd nuka grenade and bottlecap bomb damage
Not to mention the missile launcher gets ridiculous.
Also, I'm a big proponent of Scrounger. From a thread I started, it makes all other perks relating to Caps (Law bringer, Contract Killer, and Fortune Finder) kinda useless because you can sell unwanted ammo well. The extra ammo is also a huge plus, especially if you're playing Energy weapons or big Guns.
initial stats special=9 8 4 1 3 9 6 (get the intelligence bobblehead at level 2)
2 intense training Endurance 3 intense training Endurance 4 comprehension 5 intense training Luck 6 toughness 7 intense training Endurance 8 scrounger 9 commando 10 strong back 11 intense training Endurance 12 silent running 13 finesse 14 sniper 15 cyborg 16 action boy 17 better critical 18 gunslinger 19 intense training Endurance 20 grim reaper's spirit/solar powered
final stats with reily ranger armor+ledaux hocky mask+ lucky 8 ball+ant sight+all the other perks u get from quests+ alot of skill books found all skills at 100 special = 10 10 10 2 4 10 10 68 damage resistance=39ranger armor+4mask+10toughness+10cyborg+5oasis perk 33 percent chance critial with vats=10luck+3 survivor guru+5 finess+15 vats 51 poison resist=45(endurance)+6(survivor guru) 24 rad resistance=18 endurance+ 6 survivor guru 140!! action points=85(agility)+25 action boy+25 mask+5 ranger armor 490 hps=300(endurance)+10*19 level ups reily armor imo is better than t51b cuz you can repair it to 100 and it gives luck and 5 action points and 10 small guns and ledaux mask with 25 actions points is> any other helmet you can use