The DC wastelands can be a challenge. A lot of monsters (mirelurk, radscorpions, super mutant, enclave soldiers) have very high damage threshold making them hard to kill with most of weapons of Fallout 3. The most powerfull weapons of fallout 3 tend to rely mostly on high damage per second but poor raw damages.
Only a few builds seems in that context to be viable in Vanilla :
The mercenary : Shotgun build. Probably one of the easier to play :
I got as soon as level 8 a hunting shotgun from the talon mercs, however the best is still to get the combat shotgun. You can buy one on flak & schrapnel store. The combat shotgun ammo is more common because used by the raiders for the single shotgun and more rarely with the sawed-off shotgun.
Tag skills :
Guns, Repair, whatever you want (I used speech)
Special : Strength 6 Agi 5 End : 8 Int : 9 Cha : 2 Per : 5 : Luck : 5
Level 2 : rapid reload
Level 4 : educated
Level 6 : shotgun surgeon
Level 8 : toughness
Level 10 : And stay back
After that, whatever you want, more criticals and better criticals can be interesting but you must use 2 special training perks to get enough or take implants in new vegas.
I am using this one right now, it's very efficient.
My next to test is
The barbarian : 2 handed fighter
Special : Strength : 7 (get an implant or the strenght perk of those! to get 8 for the super sledge), Agi : 6 (to raise to 7 to get slayer at level 24), End 8 Int : 9 Per : 1 cha : 8 luck : 1
Tag skills : Melee weapon, medecine, whatever you want
Level 2 : confirmed bachelor/black widow
Level 4 : educated
Level 6 : toughness
Level 8 : Superslam (melee weapon 45)
Level 10 : toughness
level 12 : piercing strike (note that you need 70 unarmed for this one)
Level 14 : toughness
When you can : Purifier, Slayer
About companions : You must keep a neutral karma until you can have Sergent RL3. He is the one who will kill the targets you can't reach.
About weapons : You can find a guarantee super sledge in Satcom array NN 03.
Quests : Oasis, those, waters of life are must have.
Some other interessant possibilities : fire samurai (shishkebab with pyromaniac, better critical, more critical, piercing strike is still highly necessary), snipers are rather easy to make and are efficient, cow boys seems to have good potential too : you have many guarantee 44 magnum located aswell, hand loaded 44 ammo are quitte good at dealing with ennemies with high DT and blackhawk is not too hard to get.
The hardest build would be to rely on energy weapons. There is few ones available with high damages and good fire rate. Plasma rifles are rather poor weapons. Smuggler end have good potential but is very hard to get, the same for wazer wifle.
Only mothership zeta offer very good energy weapon. It means to complete Mothership zeta very early, I should test that too. Did anyone tried ?