Why was Reuven so distraught when he discovered that Yosef was no longer in the pit?
Rashi and Targum Yonasan: He was concerned about his father's grief.
Moshav Zekenim, Hadar Zekenim, Ba'al ha'Turim: He was afraid that his father would blame him for Yosef's death, which he would attribute to the fact that Yosef had taken over the Bechorah from him, 1 for which he had now taken revenge.
Malbim, from the Ari Zal: Yaakov was destined to father Efrayim and Menasheh; he did not, because Reuven disturbed his bed. Reuven's Mazal understood that his sin will be fixed through sons that will come from Yosef. 'But now Yosef is gone - how can I fix my sin?!' Refer to 35:22:6:9 and the note there.
It was only later that Yaakov gave Reuven's Bechorah to Yosef! Hadar Zekenim connotes that the Pasuk "uv'Chalelo Yetzu'ei Aviv Nitnah Bechoraso l'Yosef" (Divrei Hayamim I 5:1) was already known (through Ru'ach ha'Kodesh).
Why were the brothers not concerned about their father's grief - considering that even Esav stated that he would not kill Yaakov while Yitzchak was alive, in order not to cause his father pain?
Oznayim la'Torah: It was a Divine decree that Yosef should go to Egypt to prepare the way for Galus Mitzrayim - and that the brothers should therefore act the way they did. 1
The question one can then ask is how the brothers could be taken to task for the sale of Yosef? (EC)
What was Reuven's complaint, "Where will I go"? He did not tell the brothers that he planned to return Yosef!
Ohr ha'Chayim: Since I am the Bechor, Yaakov will ask me 1 to search the entire world to find Yosef. Had Yosef died in the pit, I would bring the body killed via Chayos. Now, where will I go to find him? To solve this, they slaughtered a kid [and dipped his robe in the blood].
Ha'amek Davar: Had I not suggested throwing him in the pit, I would never have allowed to kill or sell him. He was killed via my counsel. Where can I go to exile, like one who killed b'Shogeg? Hashem told Kayin "Na va'Nad Tihyeh ba'Aretz" (4:12) for killing b'Shogeg! 2