One thing I've noticed is that most players find hobby related knowledge skills to be useless or a waste of karma. If your character has only shadowrunning related knowledge skills it can serve as a detriment because you have nothing in common with people outside the shadows. Having knowledge skills pertaining to baseball, fine restaurants in Seattle, comic books, trid shows, etc is valuable because it gives you something to chat about with npcs. Having common ground is a great way to get on someone's good side and these types of things come up all the time in game. It also helps your character blend in with the masses more. Another aspect of it is realism, even shadowrunners are almost always going to be fond of activities unrelated to the shadows. Being able to watch all the Mariners games during the regular season and playoffs and actually caring about it adds depth to your character, makes them more believable, and can have an impact on how you set up your apartment, which merchandise you buy, how you dress in social settings, and so on.
I made a character once that invested a fair bit into knowledge skills and also knowsofts and linguasofts. It did set him back on the job but he was very well fleshed out and it made him a lot of fun to play, I'd say he was probably one of my best designed characters I've ever made. He also survived and turned out to be decently powerful in the end. I remember when I was a kid I was always worried about my characters losing because the GM could then do bad things to them. So I often tried to build pretty strong characters, and of course, they were less fleshed out and less fun to play as a result. Nowadays my goal is to create the best character I can, not in terms of power but in terms of how much fun I'll have playing them. This definitely comes at a cost but overall I find roleplaying much more fun this way. I no longer worry about losing, my character is how he is, for better or worse.