"¿Quién no es simpático en tu familia?"
Translation:Who isn't nice in your family?
No, the sentese means to a person in your family, not to your family. But you can use simpática if all persons in her/his family are women
'Es' is used for characteristics. So you can say 'my hermana es simpática y inteligente' because that's just her character. But you say 'está cansada y triste' because that's her state at the moment.
Simpatico is used because it is a general question which involves both genders.
Not necesarily. Simpatico as the male form of the word includes both male and female family members.