I hate to say it, because I don't like the direction the ecosystem is heading, but if I were you, I'd launch on the Mac App Store first. You just can't ignore the boost you're going to get from that avenue.

If it turns out that your plugin system is actually a big win, then you can change your mind later. And it's not an absolute kiss of death. For example, almost all of Rogue Amoeba's apps can't be made App Store compatible, but they don't seem to be hurting too much because of it.