How many rounds of peer-review do you consider appropriate for the same journal? What happens if you adjust your manuscript accordingly after the 1st round (major changes) but you receive "brand new" major comments, as if your revision had to start all over again?
This tends to depend on the paper and the journal. In my experience, it is fairly typical to expect at least 2 rounds of revision prior to acceptance, including some major revisions in the second round of reviews. At times, it seems unclear why such major concerns were not raised in the first round of reviews, but sometimes such concerns only arise after initial edits have been performed.
This can be quite a problem if you have to wait a couple of months between rounds. The worst fear is that the manuscript might not be accepted even after all the adaptations and the waiting time.
If you get additional major requests, you really don't have much choice, expect to submit to another journal instead.
In my experience, the request for a second major set of revisions happens most often when you get a new reviewer, and most journals try to avoid that.
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