Do two rounds of major revision lead to a better chance of getting the paper accepted? I submitted a paper to a prominent journal in my field. The reviewers all indicated that the paper would make a positive contrition to the field in the first round of review and asked me to make a major revision. I revised the manuscript according to their review and all reviewers indicated that they like my revision. However, one of the reviewers kept raising new issues and asked me to undertake another round of "major revision." Personally, I really feel that the new issues are not too difficult to address. However, I am wondering whether it is fair to keep raising new  (major) issues in each round of review. And, what is my chance of getting the paper accepted in the scenario described above (two rounds of major revision)? Thanks very much for your insight.
I think of requests for revision as falling into three basic categories, sorted in order of importance:


New technical results (e.g., additional experiments, more theorems)
Large-scale text improvement (e.g., reorganizing text, dealing with pervasive language issues)
Localized text improvement (e.g., improving explanations, adding references)


Of these, only a request for new results should be of concern as a possible road to rejection: for the other two, if you want the paper published, if one cares to one can typically always put in sufficient work to address reviewer comments.  It may be hard, unpleasant, and unrewarding (depending on the particulars), but this is an area where any request for revision almost always has a clear path to publication, and of a stronger paper than you started with.

Requests for new technical results, on the other hand, might or might not be something that you cannot reasonable address.  If you can address them, then it's still a clear road to publication of a stronger paper.  If you can't, however, then it's a question of scope and may be worth discussing with the handling editor to see whether they are a sine qua non for publication.

In general, however, my feeling about requests for revision, even major revision, is that they're generally good news.  Once a paper hits at least a major revision, it's highly likely to be eventually accepted if the authors just keep answering the requests for improvement, and will likely be the stronger for it.  There are exceptions (I just had one rejected by a journal for the rather unusual reason that "they only allow one revision,"), but in my experience these most frequently reflect an author who has chosen to fight the reviewers rather than to improve the paper.