Have you ever done the "run straight to Vegas" and start out as a low-level character in the big city?
Or how about starting one of the DLCs with as low-level a character as possible?
Or a character with a quirk? Such as: always drunk, or won't touch dead bodies, or won't use any chems.
I never used chems in Fallout 3 because my character would get addicted to them, and I didn't want to deal with it. Used Med-X quite a bit than everything started becoming hazy and annoying and my V.A.T.S wasn't hitting the target as well. Really got on my nerves and hacked me off. So I think chems just make you weaker. No different than having an addiction that hits you in times when you need to be focused.
I will never use chems again in a Fallout game. I'll use Stimpacs and Radaway, but nothing else.