What is the significance of Ya'akov cursing Shimon and Levi's anger?
Rashi: Even when Ya'akov was angry with his sons, he cursed, not them, but their anger. 1
Seforno: He cursed 2 their anger by lowering their prestige and their lessening their livelihood, by dividing them 3 and scattering them among the tribes. Moreover, Levi would not take over the Kehunah until they earned it, following the sin of the Golden Calf. 4
Targum Yonasan: What he meant was that the town of Shechem was cursed when they attacked it to destroy it in their powerful anger, and their fury against Yosef was harsh.
Hadar Zekenim: Arur [here] is not a curse. It means that their anger should be diminished.
Prompting Bil'am's statement to Balak (23:8) "How can I curse those whom Kel did not curse?" (Yakov's Brachos were with Ru'ach ha'Kodesh - PF.)
Which has connotations of reducing.
Part of Shimon's territory was located in the middle of Yehudah's and part among the other tribes; whereas Levi was (given forty-eight towns) scattered throughout Eretz Yisrael (Targum Yonasan).
As the Pasuk states in Eikev (10:8 [Seforno]).
What did Ya'akov mean when he stated that he would 'divide them within Ya'akov and scatter them in Yisrael'?
Rashi #1: Ya'akov meant that he would separate them from one another, in that Levi would not be counted as one of the twelve tribes.
Rashi #2: He decreed that Shimon would be poor, by virtue of their profession (Sofrim and Melamdim), 1 which also forced them to scatter far and wide to find Parnasah; whereas Levi would have to travel far and wide to collect T'rumos and Ma'asros in the granaries. 2
Seforno and Targum Yonasan: Refer to 49:7:1:2.
Rashbam: By scattering Levi throughout the land, he ensured that Shimon would be separated from him.
Rashi's two explanations seem to pertain to the two sections of the Pasuk, respectively (the first one to "Achalkeim be'Ya'akov", the second one to "va'Fitzeim be'Yisrael"). 2
His decree on Levi was more respectable (Rashi), presumably because of their elevated status. This in turn, may well have been rooted in the fact that, already in Egypt, they were known as righteous scholars (See Rashi and Ramban on Shemos, 5:4).
What did Ya'akov hope to achieve by separating Shimon and Levi?
Targum Yonasan: As long as the two brothers remained together, no kingdom would be able to stand up to them. 1
רש"י: וזהו שאמר בלעם וכו': מה הראיה משם?
גור אריה (במדבר כג,ח): כתוב "לא קבֹּה" בלשון עבר (ולא 'לא יקוב')- משמע שהיו ראויים לקללה ואעפ"כ לא נתקללו.