Bloody mess.so much fun when you shoot a guy in the hand with a BB gun and his body explodes into tiny chunks of fun.
Animal Friend. Animals will no longer attack you unless you attack them first. Really helpful if you don't want to fight Yao-Guai.
PS. If you're a high level also consider 'explorer' - it shows every map location.
Black Widow. Besides the extra dialogue options, you get a combat bonus against male NPCs, and most hostile NPCs (Talon Co., Enclave, half of the raiders and slavers) are male.
To expand a bit on the above answers: With Bloody Mess, as mentioned above, not only do you get gratuitous gore (fun!), but there is also a practical benefit of an added 10% increase in damage done by all weapons. Animal Friend's second rank is especially useful because Yao Guai and packs of Vicious Dogs will actually come to your aid during battles if they are nearby, meaning they will help you fight Deathclaws and Radscorpions (even those nasty Albino Radscorpions). Black Widow is essential if you have a female character: right from the get-go you can seduce people like Mister Burke (he sends you love letters [lol] and leaves Megaton alone) and during the "You Gotta Shoot 'Em In the Head" quest, you can get Dukov's key for free. Along with all of the aforementioned perks, another one I'd personally recommend is Entomologist, which increases damage inflicted on insect enemies like those stupid ants (all variations including Fire) and Radscorpions. I can't count the number of times I encountered them in random encounters in the Capital Wasteland... argh.
Including the DLCs, ghoul ecology from Point Lookout is great, but mostly because it's bugged and gives you the bonus against everything, not just ghouls. And you get it from an in game event, so it doesn't take up a perk choice when you level.
Grim reaper if you use VATs alot, the combination of that, a shotgun and a small room anilhiltates everyone in the room quickly