I've seen people re-write extensively and still be turned down. Then they send out the revised ms, and get more suggestions that lead back to the first version. That gets turned down too. The author is left confused, demoralised and derailed. Now they have three versions, and they have no idea which is best. Or even which is closest to their original vision.
Some changes are more intrusive than others. Plot changes are often quite easy to accommodate - I've done this several times for foreign editions of my books. I've also made character changes. But this was for someone who'd bought the novel. Would I for someone who hadn't paid up front? I'm not sure.
A former student has an agent (but not yet a publisher) and is constantly re-writing stuff for this agent, sending out her new novel 5 pages at a time for comments. This seems unhealthy to me. I asked my editor what she thought about their arrangement and she said she'd be very wary of taking on someone who a) needed so much editorial support b) hadn't got confidence in their own writing and c) might have lost their own authorial voice in the re-writes.
I have to say that my former student is thrilled with the situation and I hope it works out for her, but it's not one I'd be happy with. Unless all the feedback you're getting points in the same direction I think you have to have courage of your own conviction. It is YOUR novel after all.