Why should Avraham not worry about Yishmael having strayed from the right path?
Targum Yonasan: Because Hashem had discredited him from being his heir (and so should he).
When Hashem told Avraham not to feel bad about sending away Yishmael and Hagar, why did He refer to the latter as "his maidservant?
Seforno: He was referring to Sarah's instructions (not specifically mentioned) to expel them with signs that they were slaves. 1
What did Hashem mean when he instructed Avraham to listen to Sarah's voice"?
Rashi: He meant that he should follow the voice of her Ru'ach ha'Kodesh, since he was secondary to her in prophecy.
What is the significance of the final phrase in the Pasuk?
Seforno: 'Because Yitzchak will be called your seed, and Yishmael and his sons will be slaves to him'.
Rashbam: 'Because the B'ris that I established with your children to give them the land of Cana'an ... I promised you with regard to Yitzchak'.
Targum Yonasan: 'The son of this maidservant will not be considered your offspring'. 1
Similarly, the Gemara in Nedarim (31a) Darshens "be'Yitzchak", 've'Lo Kol Yitzchak' - to preclude Eisav (Rashi, Vayeitzei, 28:15).