4:16 – “Cain left the presence of Hashem..” – He departed in (pretended) humility as though he could deceive the Most High (Rashi). It is obvious that Cain did not actually deceive God. God ‘sees the heart’ and was fully aware that once Cain received clemency, he would resume his evil ways. Nevertheless, Cain claimed sincerity and God allowed him a degree of clemency assured that in the course of time Cain’s wickedness would become apparent to all. At that time, God would exact full punishment (Harav David Feinstein).
“..settled in the land of Nod” – Nod means ‘wandering’ – the land where exiles wander about. However, he did not find any rest there for his fate was to be a ceaseless wanderer. He is identified with this region, however because it was there that he spent most of his time; his family resided there; and it was there that he would return periodically during his wanderings (Abarbanel).
“..east of Eden.” – To the east of Eden, where his father had been exiled when he was driven out of the garden (3:24). Notably, the eastern region always forms a place of refuge for murderers, for the cities of refuge that Moses later set aside were also to the east, ‘the place of sun-rise’ (Deuteronomy 4:41)
4:17 – “..a city-builder,” – It does not say, he built the city. The term ‘builder of a city’ implies that his personality is being described. Cut off from the earth, Cain was left only with his own intelligence and talent which he utilized to build cities. Urban life, unlike rural life, ‘cultivates’ its inhabitants. Hence, the following verses list the sophisticated skills that were developed in his inhabitants (Hirsch).
“…named the city after his son..” – Thus proclaiming that he did not build it for himself because he was cursed and a wanderer. Rather it would be as if Enoch had built it for himself (Ramban).
4:19 – This verse could simply have said ‘and Lamech begot Jabal … etc’ listing the births of generations as it does in succeeding chapters but the Torah goes into the narrative (verses 23-24) to inform us that God kept the promise that ‘vengeance shall be taken on Cain after seven generations.’ For after Lamech had children – the seventh generation – he arose and slew Cain (Rashi).
4:22 – “..the sister of Tuval-Cain was Naamah” – Her name, meaning lovely, is mentioned because she was the wife of Noah, and her deeds were lovely and pleasant (Rashi). She was famous and, being a righteous woman, she gave birth to righteous children. Thus, a token remembrance of Cain was left in the world (Ramban).
4:23-24 – Lamech’s Plea. Lamech was blind and his son Tubal-cain used to lead him. One day, Tubal-cain saw Cain and mistaking him for an animal, he bade his father to shoot an arrow, which killed Cain. When Lamech realized he had killed Cain, he beat his hands together in grief and accidentally struck his son, killing him, too. This angered his wives who refused to live with him, and he tried to appease them. He demanded that they obey him and come back, for, he asked, since he had not killed intentionally, could he be considered a murderer? As to their fears that God would punish him, he contended, “If the punishment of Cain, an intentional murderer, was delayed until the seventh generation, surely my punishment will be deferred many times seven because I killed accidentally!” He used the number seventy-seven to denote many times seven – a long period, not meaning exactly seventy-seven (Rashi).
4:25 – “And Adam knew his wife again..” – This occurrence happened previously but first the Torah completed the entire narrative of Cain and Abel and now returned to detail the generation of Seth and his descendants. This is an example of ‘the Torah does not concern itself with chronological sequence’, the Torah arranges each general topic (such as the story of Cain and Abel) separately (Aderes Eliyahu).
Adam saw that Abel was dead, Cain was cursed, and Cain’s descendants had gone in evil ways. He ‘knew’ his wife again – after a separation of 130 (Midrash) – to ensure that worthwhile forebears of mankind would be produced (Malbim).
4:26 – “Then to call in the Name of Hashem became profaned.” – The generation of Enosh introduced idolatry, which was to become the blight of humanity for thousands of years. By ascribing God-like qualities to man and lifeless objects, they created the abominable situation in which to call in the Name of Hashem became profamed (Rashi).
Note: Rambam thought this so very fundamental that he wrote at length:
In the days of Enosh, the people fell into gross error, and the wise men of the generation began to give foolish counsel. Enoch himself was among those who erred. Their error was as follows” ‘Since God created these starts and spheres to guide the world, set them on high and allotted them honor, and since they are ministers who service before Him, they deserve to be praised and glorified, and honor should be rendered them. It is the will of God, blessed be He, that men should aggrandize and honor those whom He aggrandized and honored – just as a king wants respect to be shown to the officers who stand before Him, thereby honoring the king. When they conceived this idea, they began to erect temples to the stars, offered up sacrifices to them, praised and glorified them in speech, and prostrated themselves before them – to obtain the Creator’s Favor, according to their corrupt notions. This was the root of idolatry, and this was what the idolaters, who knew its fundamentals, said. They did not however maintain that, except for the particular star which was the object of their worship, there was no God. All knew that He alone is God; their error and folly consisted in imagining that this vain worship was His desire.
In course of time, false prophets arose who asserted that God had commanded and explicitly told them, ‘Worship that particular star,…offer such and such sacrifices to it. Erect a temple to it. Make a statue of it, to which all the people – the women, children, and the rest of the community – shall bow down’ …. They began to make figures in temples, where they would assemble, bow down to the figures, and tell all the people that this particular figure conferred benefits and inflicted injuries, and that it was proper to worship and fear it.
So gradually the custom spread throughout the world to worship figures with various types of worship, such as offering them sacrifices and bowing to them. As time went on, the honored and revered Name of God was forgotten by mankind, vanished from their lips and hearts, and was no longer known to them. All the common people and the women and children knew only the figure of wood and stone, and the temple edifice in which they had been trained from their childhood to prostrate themselves to the figure, worship it, and swear by its name. Even their wise men, such as priests and the like, also fancied that there is no God save for the stars and heavenly spheres for which the figures were made.
But the Creator of the Universe was known to none, and recognized by none, save a few solitary individuals, such as Enosh, Methuselah, Noah, Shem, and Eber. The world moved on in this fashion, until the Pillar of the World, the Patriarch Abraham, was born (Hilchos Avodas Kochavim 1:1,2)