I don't simulate a full FPGA design but only separate modules with well defined interfaces. So I have separate projects for simulation and synthesis/test/debug. I never call modelsim from Quartus.
As for my project structure, we heavily use version control at my job (Subversion... I'd like to move to Mercurial but it has been hard enough to make everyone move from "cp -r" to subversion already ;) ). So I have even separate folders for source code between simulation and synthesis. My Quartus project uses subversion externals to point to each module I use and I use Subversion to synchronize between my simulation and synthesis folders. It needs some getting used to but I have a lot better control now over module versions and update. It makes it also easier to work on a new version of a module in Modelsim without disturbing an ongoing Quartus project.