"And Yaakov became very frightened, and it distressed him" (Vayislach 32:8.) Rashi explains that Yaakov had two different emotions. On the one hand, he was frightened that Esav might kill him, while at the same time, he was also distressed that perhaps he might have to kill others in order to save himself. Why was Yaakov so concerned that he might kill others? After all, the posuk says, "When the wicked perish, there is joyful song" (Mishlei 11:10.) Moreover, Yaakov knew that Eisav wanted to kill him. Chazal say, "If someone is coming to kill you, preempt him and kill him first" (Sanhedrin 72a.) Why then was Yaakov so distressed?
Rav Moshe Feinstein (Darash Moshe) suggests that Yaakov was pained by the prospect that he might have to kill others to save himself because such an outcome was not truly necessary. Yaakov knew that Hashem could easily save him without forcing him to harm other people. Eisav could simply decide to leave Yaakov alone and not attack him and his family. But if Hashem were to save Yaakov only by having him kill other people, that would demonstrate that Yaakov Avinu was deficient in some way and did not deserve to be saved in a more pleasant manner. It distressed Yaakov to consider such a possibility.
This is similar to one who finds tzara'as in his home. The Torah says that when Klal Yisrael come into Eretz Yisrael, Hashem will place a nega tzara'as on the walls of their homes (Vayikra 14:34). Rashi comments that this tzara'as is actually a positive development because by demolishing the home as part of the purification process, the homeowner will uncover treasures that the previous non-Jewish owner hid in the walls of the home. But there is also a negative element in this tzara'as because if the Jewish owner were not guilty of a sin, then Hashem could have given him wealth by other means. The fact that he receives his wealth through a tzara'as affliction proves that he is somewhat guilty and in need of an atonement. Similarly, if Yaakov Avinu would have to resort to saving himself by killing other people, that would show that he was not worthy of being saved in a more pleasant way. And that may have been the cause of his distress.
But perhaps Yaakov Avinu was upset for a different reason, namely that even if killing others in self-defense is justified, nevertheless the act of murder itself, even when warranted, has a negative effect on a person. The Sefer HaChinuch (#16) writes that the Torah prohibits the breaking of the bones of the korban Pesach because "ha'adam nif'al k'fi p'ulosav - a person is affected by his actions." A prince does not break bones when eating. If Klal Yisrael were to break bones when eating the korban Pesach, that might ingrain within them a lowly spirit. The Torah therefore prohibits breaking the bones of the korban Pesach to ensure that Klal Yisrael will act like royalty, and that will reinforce within them an appreciation of their elevated status.
The Torah, in a different context, alludes to the powerful effect that negative behavior can have on a person. After the Torah dictates that an ir hanidachas (a city which worships avodah zara) must be destroyed, it adds that one may not derive any benefit from the rubble of the city "so that Hashem will turn back from His anger, and He will give you mercy" (Devarim 13:18) Why does the Torah emphasize that Hashem will give you mercy? The Chofetz Chaim explains that it is only natural that one who murders, even when he is obligated to do so, will become more cruel and insensitive. The Torah promises that this will not happen to those who obey the command to destroy the ir hanidachas. They will not be adversely affected by their actions, rather Hashem will reinforce within them a sensitivity for human life, and He will ensure that they remain merciful and compassionate people.
Perhaps Yaakov Avinu was distressed that he might have to kill in order to save himself because he feared that without special protection from Hashem, he would be negatively affected by the act of murder. Even if he were technically permitted to kill Eisav and his men, going through that process would make him a more callous and inconsiderate person. Yaakov davened that Hashem should save him not just from the hands of Eisav, but from any negative effect to his character that an encounter with Eisav might generate. This is the way of a righteous person. Not only is he careful with his actual deeds, but he exhibits a heightened sensitivity to the secondary ramifications of his behavior as well.