You see that when man separates from a settled area, he finds himself detached from his “place,” He is then deprived of the special protection provided him, according to the order of the world as created by G-d. This is why a place is called “makom,” (from the same root as “kiyum,” which means survival or existence) for is one’s existence is dependent upon and provided by a suitable environment.
When man departs from a place which is inhabited, he finds himself out of his “makom.” It is the “makom” which provides natural protection for his existence, and being out of that place deprives him of that system of protection.
Furthermore, man is protected when he is within a “klal” (a unified community). Even if man is alone in his home (seemingly not part of the klal at that moment) being in a city with many other people includes man within the system of protection afforded to a community.
Therefore, the Mishna teaches specifically about a person walking ALONE on the ROADWAY. He has left the protective system of this natural place (by being on the road). And he has isolated himself (albeit temporarily) from all other people (by being alone).
(The word “derech” means a main roadway connecting two different places, rather than a local street.)
There is a mystical concept about the protection accorded two people together (as opposed to one person by himself) as seen in the following lesson (Berachoth 43b): To one person, [the demon] appears and causes harm; to two people it appears, but doesn’t cause harm; to three people it doesn’t even appear.
Man, created “b’tzelem Elokim,” as a reflection of the Divine, is worthy of being above all other creatures, as we are taught (Shabbath 151b, Sanhedrin 38b): No animal can have control over man unless man becomes like an beast, as it is written (Tehillim 49:21) “Nimshal k’beheimoth nidmu. (One who is ruled over, is compared to a beast.)
(This is an example of the Rabbis departing from the contextual and literal translation of the verse to extract an ethical lesson. One studying the verse sees that its literal translation is “[Man without understanding] is compared (“nimshal”) to silenced (“nidmu”) animals (beheimoth)” However, the word “nimshal,” also means “be ruled over,” the passive form of the root “limshol.” The word “nidmu” also means “compared to,” from the root “domeh,” meaning “similar.” These kinds of Rabbinic interpretations aren’t simply poetic license, but reflect an understanding that connects the contextual, literal translation with the deeper, modified understanding of the text.
(The Maharal explains a number of times that the word “drash,” which we usually associate with an interpretation that ignores the literal meaning of the text to create some kind of forced “word association,” in fact comes from the word “demand, or “thorough inquiry.” See Devarim 13:15 and Rashi. Also Devarim 19:18. The drasha is the meaning of the text as it demands to be understood if one probes the text thoroughly and deeply enough to reach its true meaning. See Be’er HaGolah, the beginning of Be’er III, pg. 44 in the Hoenig edition and page 220 in the Hartman edition. See also this section in the English translation of Be’er HaGolah by Rabbi Yitzchok Adlerstein.)