To tonal topic, sure, it might sound different, but it will sound different for you anyways, regardless of the amp state, because no one knows what output method was used by the author if you download a preset. Since i've got the HD Desktop and use headphones most presets have a way to less bass for my taste. And that might result from my output device. So i mean, interchanging presets is a nice feature, but you'll most likely have to manaully fine tune them anyways.

I'm not sure, what you mean by "it will work fine". It will certainly not keep your settings if you switch from a Pre to a Full Amp or vice versa  if you changed the settings (i.e. you've loaded a preset). Somehow, for me, it always fetches the settings for a specific amp i've had upon booting the device.  Just try it, for me, it works somehow, but certainly not nice. Maybe it is different on the HD 500, i don't know.

So, if you run into the same problems, you can tryout to set the pre amp to a full amp directly in the preset using my tool (or vice versa): http://www.jzab.de/content/pod-hd