Like others said, depends on your build
Here's a few suggestions
Melee or Unarmed - Super slam makes this character. Worth getting, even on unarmed (you need 45 melee)
Unarmed - piercing strike
Melee or Unarmed - toughness can help as you will be up close and personal a lot.
Guns - get hand loader asap; you can make better ammo
Sniper character - better criticals combined with finesse
General - comprehension (very powerful if you want to make a lot of science/barter/speech/lockpick skill checks more quickly and easily)
I'm also avoiding the vats perks as I don't use it as much as fallout 3.