The biggest difference between the two families are the two latter mentioned elements: the children and talking non-humans.
Furthermore, the Griffins’ alcoholic dog, Brian (MacFarlane, essentially, as himself) serves as the voice of reason, while the Smiths’ German-accented goldfish, Klaus (Dee Bradley Baker), and extraterrestrial live-in guest Roger (MacFarlane) also have their vices and voice of reason in less helpful ways.
While on Family Guy, Meg (Mila Kinus) is the Griffins’ black sheep, Chris (Seth Green) is only slightly smarter and slimmer than his father, and Stewie (Seth MacFarlane with a British accent), is an infant of genius intelligence hellbent on world domination, liberal teen Hayley Smith (Seth’s sister, Rachael MacFarlane) never cowers from standing up for herself and her brother Steve (Scott Grimes) is an average high schooler who wants to prove he is more than a dork.