This is why you need either a mentor or a supervisor who understands not only the technical aspect of the subject matter, but also the "politics" of the system. One tends to start learning and have a feel for it after one is in the field for a while, but before that, a consultation with someone in the same field is the most appropriate thing to do.
Journals such as Science, Nature, and even PRL require a paper that has a significant and extraordinary impact, even beyond the narrow field of study of that area (this is true for Science and Nature). So unless your work has that caliber, your manuscript will not even make it pass the editors who, I think, reject more than half of the submission even before they get to the referees.
Even for specialized journals, you still need to know or have a feel for what level of importance they would want. I have submitted papers to Phys. Rev. B, and often, they were sent to 3 referees, which is a common number for PRL, Nature, and Science. Yet, it has almost the same degree of scrutiny as the other more "prestigious" journals.
The best thing you can do is familiarize yourself with the journals that you wish to submit to. Check if they have published topics in your area, and if the caliber is of the same as what you will be reporting. You want a journal that people in your area are most familiar with and cited often.
Zz.