The idea that the harlot represents Roman Catholicism, a belief that became popular in the days following the Reformation, for obvious reasons is tied closely to the historicist view in general, which sees the Book of Revelation as describing the whole of church history. With the continuing demise of historicism, however, proponents of this interpretation have become few and far between. This position is probably best understood as a natural Protestant outgrowth of the Reformation controversies.
The Apocalypse would be portraying Catholicism as an institution that at one time in history constituted the very people of God, but at some point forsook her God, presumably by corruption and abandonment of the gospel the primary contentions of the Protestant Reformers.
One of the simplest, yet strongest clues that Jerusalem is to be understood as the harlot of Babylon is that John seems to give the answer away directly to the observant reader in a couple of key places in Revelation. At the end of chapter 17, the interpreting angel tells John the identity of the adulterous woman explicitly: The woman whom you saw is the great city which has dominion over the kings of the earth (hJ gunh h}n eide" e[stin hJ povli" hJ megavlh hJ e[cousa basileivan ejpi tw'n basilevwn th'" gh'"). This phrase the great city seems to be set forth with the assumption that the reader knows what city that would be, and the phrase is tossed around several more times in this passage Moreover, the phrase appears to be used quite exclusively in the book of Revelation. Outside of this passage, in which it occurs many times, all of which clearly refer to Babylon, the phrase only appears twice in the rest of this twenty-two-chapter book. The first, and most important occurrence of the designation the great city is in 11:8, which reads, And [the two witnesses] bodies will lie in the street of the great city which is spiritually called Sodom and Egypt, where also their Lord was crucified (to ptw'ma aujtw'n ejpi th'" plateiva" th'" povlew" th'" megavlh" h{ti" kalei'tai pneumatikw'" Sovdoma kai Ai[gupto" o{pou kai oJ kuvrio" aujtw'n ejstaurwvqh). This verse is extremely significant. In it, we have two major pieces of information relevant to our study.
First, it is all but indisputable that the great city as identified here is Jerusalem, where also their Lord was crucified. This alone sets a powerful precedent for the term before we come to chapters 17 and 18. This term is not used carelessly for many cities in the book, but rather only twice without explicit reference to Babylon. It is hard to imagine this reference not ringing in the ears of the original audience when they would arrive at 17:18. It would easily be the most natural step, if a somewhat shocking one.
Secondly, the writer also sets a precedent for using metaphorical names for Jerusalem, specifically names of Israels ancient enemies. This tells us two things: we should not be surprised if he does it again, and Jerusalem is being painted in a very negative light in Revelation.
A similar occurrence of the phrase the great city is found in 16:19, where again we have a vital clue to the identity of the harlot who appears later. The verse reads, And the great city was split into three parts, and the cities of the nations fell (kai ejgevneto hJ povli" hJ megavlh eij" triva mevrh kai aiJ povlei" tw'n ejqnw'n e[pesan). The key point to be made here is that the great city is apparently contrasted with the cities of the nations. It could be that the great city is merely one of the cities of the nations, but it seems more likely that the two are to be distinguished; we are not told that the other cities of the nations fell, just that the cities of the nations fell, as distinct from the great city. The juxtaposition of this phrase with the cities of the nations suggests that it is not a Gentile location, such as Rome. This also becomes more probable in light of the lexical ambiguity of the Greek. For neutralitys sake, the translation given above has simply rendered tw'n ejqnw'n of the nations. In Greek, of course, the term may be translated either in this manner or more specifically as of the Gentiles. The NET Bible notes this as an alternative translation, and if we take this option, the text is even more telling. In this case the great city would be juxtaposed against the cities of the Gentiles. In light of the last use of the great city, in which it was identified as the place where also their Lord was crucified, this does not seem unlikely. What makes this especially significant for study is that this verse may bridge the gap between 11:8 and 17:18 in that the remaining portion of 16:19 fills out the image of this great city by identifying it explicitly as Babylon.
In addition, this interpretation can be further validated by the Old Testament background of the citys fate in this passage. As several commentators have recognized, the splitting of the city into three parts seems to echo Ezek 5:15 in which God has the prophet divide his hair into three parts as a depiction of coming judgment upon a city, specifically, the desolation of Jerusalem, which will occur in thirds. Taking together the precedent of Rev 11:8, the contrast with the cities of the nations/Gentiles, and the background of Ezek 5, we have very compelling reasons to think 16:9, like 11:8, may be referring to Jerusalem as the great city. Not only that, the great city is here also clearly connected to the name Babylon. Again, these are the only two references to the great city in the book before we get to chapter 17. There is no other great city to be found in the Apocalypse, no other precedent to follow. If Jerusalem is not the harlot, it is worth asking at this point why John, who uses the phrase the great city so colorfully in chapters 17 and 18 has been so uncareful as to let it slip at two other places in the book, both of which would likely lead one to see Jerusalem as Gods enemy, if not Babylon itself.