First of all, if I play in a town, I have to edit it first. I can not play in any town as it is in its default state without going nuts, as I have all the expansions and a ton of store content, and I dislike the inefficient layouts. Every time I redesign my acceptable version of Sunset Valley, it takes so long that my husband picks on me for spending so much "play time" getting ready to play the game. Between that and my need to have my NRaas stuff set up just so, means I pretty much stopped bothering with challenges some time ago, because I find the game too un-fun without my favorite mods.
There are certain sims that always get makeovers, especially in Sunset Valley, at 8:00 AM on starting day right after I select my household, because I can't bear to see them in their default outfits even if my played sim will never interact with them. I'm trying to break that habit, as a save file where I made over a ton of SV townies prior to starting grew to a huge size of 498 MB before I even played it. So now I try to narrow it to the worst offenders, my favorites, or ones my sims end up interacting with a lot.
Every time an original townie has a child with another, I load it into CAS when it turns into a toddler so I can see what the genetics did. If it's a "just for the fun of it" file where I am play testing a lot or trying out a new feature or skill I'm unfamiliar with, I will troll my own town by using Master Controller's pollinate command just to watch the "red haired baby" messages fly in when the children are born, and then I will age them with cheats and pop them into CAS to see how the genes combined.
About 75% of the time I have a sim at University, he or she is in the science and medicine career and ends up a big nerd with a few rebel points. The other times I have played technology or art, and business once or twice for certain sims. I have never once sent a sim through the physical education career or gotten a jock higher than level 4 because I lose interest.
There are certain couples amongst townies that I ship and will get irritated if story progression breaks up, no matter who I am actually playing in the game.