What is the significance of the fact that Esav married Yishmael's daughter?
Bava Kama 92b: The fact that Esav ha'Rasha married the wicked Machalas is the source of the saying ,'The poor-quality date-palm went across to join forces with the barren tree.' 1
Oznayim la'Torah: When he saw that Yitzchak blessed Yaakov with children, he understood why. This made him jealous of Yaakov and prompted him to improve his ways - so he married his uncle Yishmael's daughter. 2
What is the significance of the name Machalas? Targum Yonasan and Bereishis Rabah 67:13 say that her real name was Bosmas (see Bereishis 36:3)!
Yerushalmi (Bikurim, 3:3): The other two are a Ger who converts, and someone who is elevated to a high position - such as a king or a Chacham.
What is the significance of the fact that Machalas was the sister of Nevayos?
Rashi (from Megilah 17a): To teach us that Yishmael died then, and her brother Nevayos married her off in his place. 1
Rashbam: Because he was the oldest brother. 2
Malbim: Nevayos was a Rasha, and children generally are like the mother's brother - even so, he married Nevayos' sister.
Rashi: From this we infer that Yaakov was 63 at that time, 14 years before he came to Charan! He must have spent 14 years in the Yeshiva of Ever (See Rashi).
Why does the Torah add "Al Nashav"?
Rashi: To teach us that he added an evil woman to evil women. Even though Esav saw how much Benos Kena'ani pained his father, he did not divorce them.
Why is there a Pesik (a line, signifying a break in the Pasuk) after "Machalas"? And why must the Torah say that Yishmael was Ben Avraham?
Ha'amek Davar citing a Midrash: This teaches that he went to Yishmael to entice him to kill Yitzchak (refer to 27:41:2:2). Yishmael died, and Esav repented and married Machalas, for she was Avraham's granddaughter. The Pesik shows that it was unlike he had initially intended.
Why does it say "Lo l'Ishah"?
Ha'amek Davar: He trained her to go in the ways of his house, that she should help him. He thought that this will appease his parents.
QUESTIONS ON RASHI
Rashi writes: "'Sister of Nevayos' - We derive that Yishmael passed away after her betrothal...." But perhaps the verse merely teaches us which wife of Yishmael was her mother?
Gur Aryeh: Even if Machalas and Nevayos shared the same mother, we would still have no idea who that mother was!
Rashi writes: "Yishmael passed away after her betrothal but before her marriage(Nisu'in), and her brother Nevayos married her off." But perhaps a long time elapsed between the betrothal and marriage; in which case we can no longer calculate Yaakov's age when he received the blessings?
Gur Aryeh #1: Esav surely married Machalas immediately, because his intent was to show his father that he had married a worthy woman.
Gur Aryeh #2: Even for a Besulah, Nisu'in is postponed for twelve months at most.