Unarmed in Fallout 3 (yeah, I know). The scaling between 20 and 100 amounted to about 3-5 points of extra damage depending on weapon (bare hands got the least, power fists and deathclaw gauntlets got the "most"), but the Iron Fist perk, which had no required skill level, increased damage by a flat 5 points with 3 ranks, so the optimal unarmed setup was actually with minimal investment in the associated skill.
Champions: Return to Arms had elemental weapon buffs for the wizard class which was cool in theory, but the buffs were actually bugged and would override any enchantments or socketed effects the weapon already had and then would permanently remove those effects when the buff ran out.
Using unarmed characters were radiated poop, compared to how the skill was used in F2 – you can tell the developers didn't give a damn for players interested in focusing on this skill.
In F2 you can kick enemies balls with aimed attacks, resulting in hilarious float texts.
Face boxing stars in Reno, or a master and their many apprentices in San Fran ring. Or a muttie inside a NCR bar. To name some points of interest for unarmed builds, to gain exp./money.
Some NPCs will try to flee if you break their limbs, use this to your advantage during big battles.
You can destroy locked doors by kicking/punching them, in certain areas.
You can "dig" holes in the torso of everbody, if you take Bloody Mess. Even young humanoids (it's no surprise some regions didn't accept an uncensored Fallout 2).
Silent kills, with bare hands/feet, if you don't want to go guns blazing. Taking Slayer is not a bad idea, if that's up your alley (for more critical blows).
Jinxed & Unarmed go well together. You will not constantly run out of ammo because you failed in a roll check, friendly fire permanent/temporary companions, etc. Now that I think about it, it would probably be decent with Throwing, (if Throwing wasn't poop, that is), as well: Even if you explode the item on your hands, it should not be a significant loss (like destroying an alien blaster). If you haven't tried it, yet, give it a try.
I can see myself starting another playthrough, mainly using unarmed for combat. I can't say the same thing for Fallout 3.