Just for .esp mastering, you understand, and never actually editing the .esm-flipped files beyond the flipping.

Yes, it is safe. Wrye Bash makes it very easy. I currently use the Copy to ESM option just because it leaves my ESP intact and there is no need to flip it back to keep working. Just copy it again to test. Simple and easy. There is a new tool on the horizon. TESVGecko is in its first useful beta form over at Dark Creations. http://www.darkcreations.org/forums/files/file/388-tesvgecko/ Among other things, Gecko will give you a true ESM master instead of a false master if you need that.

I do the same as ch0k3h0ld, though I use a different method.

I copy my esp and make it into an esm for testing. Then I still have my intact esp for working and I just recopy it each time I need to test the updates.

While on this topic, is it possible to make an ESP require another ESP?

I have my no perks version of my hunting mod, and I want to make an addon esp for it that adds some perks and abilities, that requires that no perks version.

Yes. Just flip the esm bit in the esp you want to master from. Then select it as well as your other plugin in the CK, or make a new plugin. When all done, you can flip the esm bit back off. The game itself doesn't care about the master bit - just the master list. The CK DOES care, and if the esm bit isn't on, all your edits that reference the esp master will be lost when you save/exit the CK.
Just remember to flip it back on when making changes! Depending on how flipping the bit on affects your load order, you may be able to just leave it on until you're done with the project.