Penny is an obvious case of reverse-flanderization because she was the opposite of the typical nerds. When the show started appealing more to the common crowd and had to go beyond its original plot, it was obvious Penny had to be more than just a plot device centered around looks. Same happened to the guys.
Most of the later episodes where the focus isn't on Leonard and Penny, they are mostly about sex, or Penny asking Leonard whether something Sheldon said was a burn.
Howard is another obvious case. Goes from stereotypical creep to a more complex character and gets a crazy amount of screen time to deal with his issues. Then later on, he's mostly a whipped husband (largely caused by Bernadette being flanderized), but they give him some screen time where he's more than just a doormat for wife and a snark to every other male character except Leonard.
Most of the other main/recurring cast members have similar cases or go straight from A to C and skip B.
