Effectiveness is dependent on your goals. If you want'em dead "like, right freakin' now!" then a headshot with a massive caliber might be your best option. On the other hand, if you're in the "trying to send a message to a group" sort of thing I can see where an airgun with a dart like they use to anesthetize animals (only loading the dart with something lethal but slow acting) would be the option of choice.
As for the difficulty of making them...oh, puh-lease...hollowpoints, poison, and a candle. Child's play, workbench not needed.
Alright, so judging by the lack of suppressors i've seen.. I'm guessing this won't be available as a mod in the game, at least not for pistols, or the hunting rifle :meh:
Theres still hope for AR's, but really.. I loved the standard hunting rifle in FO3 (until even Ole Reliable got outclassed, therefore making it not very useful)
Hunting rifle with scope, extended mag, and silencer FTW!

Stupid rare .308 ammo.