You have questions? Do you constantly miss #askagent sessions on Twitter? Is it impossible, despite a hundred Google searches, to find an answer to your question? Then you've come to the right place. Ask a question either on any "Agent Answers" post or on Twitter, and I'll answer as many as I can. My answers will be subjective and should not be considered applicable to every agent (though I do like to assume my opinions are the majority).
Question: If we receive a "NO" and make a significant rewrite, is it worthwhile resubmitting?
Answer: That depends. If the agent rejected you based on the query, they're probably not interested in your concept. If you had 10 or so pages attached and you think your beginning is way better (and way different), you'll only be wasting thirty seconds of your time to send it and a few minutes of theirs (or their interns) to read it (two seconds to reject it). If the agent read a partial or full from you, it's probably really worth your time, at least, to try. I personally try to be very straightforward about requesting a revised ms. If I'm no longer interested in the concept, I'll just say no. If it still has promise, I'll go ahead and take a look.
All that said, I don't like to see five resubmissions for one project. Don't do that. One resubmission should be your max. I'd rather see you branch out and attempt new projects. I'm not saying "Give up, you suck!" I'm saying, "Know when your horse needs to take a break--he might not be dead, but he might be wheezing pretty heavily."