I usually don't mess with their genetics. One prime example where I did was with the Delgato family's daughter. Once she grew up into a teen, her nose-shape was unusually large. Neither of her parents have that type of nose, so I fiddled with it slightly. She was and still is cute, but I prefer it when sims actually have physical characteristics that fall in line with their family members.
It's kinda why I feel that she wasn't born in-game and was made by the Sims team. Another sim like that was Arlo Bunch from TS3. He looked nothing like his parents or even siblings outside of the blonde hair, imo.
