Of course! That is no good to hear.
-- In terms of least-memory/processor-usage, when should I break up one prototype PAGE into several PAGES?
The largest factor is usually Widgets per page. The more you are willing or able to break up pages the faster it should be. I believe our product support generally recommends about 500 Widgets per page, but we try to optimize for many more than this. However, this includes Widgets in Dynamic Panels, Masters and Groups. Also, any Widgets unplaced on different Adaptive Views, if you are using them, can have an impact.
-- In terms of least-memory/processor-usage, when should I break one prototype FILE into multiple FILES?
Generally overall file size doesn't play as large of a role in general use performance. If the file does get very large saving, loading, and first opening of the file can start to suffer in performance. How large are you dealing with? It generally shouldn't have a huge impact (besides saving and loading) until you are getting to the 100MB+ range. You could try turning off auto-save backups to see if that helps. 'File -> Backup Settings...'
-- How much do GROUPING and NESTED GROUPING of widgets slow down Axure?
Groups and heavy nesting were definitely an issue in some earlier releases and betas of 8. If you keep on the latest releases though, they should have minimal impact unless the usage is an extreme case. Generally a couple hundred groups, nested 3 or 4 down even, should be manageable from a performance standpoint.
-- How much do DYNAMIC PANELS, and NESTED DYNAMIC PANELS slow down Axure?
Dynamic Panels and nesting generally won't matter too much, except in the fact that you can quickly up the Widget count referred to above. If you have 500 Dynamic Panels all with empty states, it won't be too bad. However, more likely a giant state can get duplicated and that will quickly bloat the Widget count.
-- Does using MASTERS, instead of the same widget/graphic multiple times, save on processor/memory?
Masters could help and are good to use anyway for future editing of the project, however besides some edge cases, I believe things should be cached at a lower level and heavy usage of Masters won't have significant impact over the other items discussed.
-- What interactions are the biggest processor/memory hogs?
By interactions are you referring to our Interactions in the Properties Pane? These shouldn't matter too much, but using large Repeaters which are heavy in Interactions can cause so pretty significant slow down.
General tool interaction, the heaviest hitters are going to be switching pages, loading and saving. Generating and previewing prototypes (which can also cause loading and saving) will also hit it pretty hard. But normally none of these should have an issue unless dealing with huge pages. Do you have a feeling for how large your pages are getting or think you have a sample you could send in?
-- A great Mac-specific improvement would be for Axure to NOT ask if I want to save a file, if I've only opened it and looked at it, not having made any edits.
It definitely shouldn't be asking you to save every time. It will do this if you are working on an unconverted earlier version of a page. Once you open and save it in your current version it should no longer ask you this. This is on a per page basis, though. Are you working with a normal project or a team project?
We are still working on optimizations and hopefully will be rolling out a few in the coming weeks and months. I'll let you know as those go live and if it doesn't seem to be helping maybe we could set up a screen share or similar to help try to get to the bottom of things.