If you're getting your water from the city, then it's been treated with chlorine and heaven only knows what else. It should be comfortably clean, even if you leave it sitting around in the pipe for a while. I figure you'd be more likely to get an off-taste from the plastic than a some kind of nasty disease. Now, if you've got well water, that's another game entirely.

For what it's worth, my house, which was built from the ground up with PEX, has everything from the entire house converging on a central manifold, just like you would do with network cabling. This has the benefit that you can centrally turn off the water to absolutely anything in the house. Very convenient.

I would consider doing the hot water runs with pipe insulation. It's cheap, and it will conserve at least some of the heat energy. If you're planning to do a hot water circulator for instant-on hot, then this sort of insulation becomes even more important. (And it also guarantees that you're not just doing a simple star-shaped topology any more.)