Would there be any disadvantage to say... running it at 2880x1800 with no scaling, and then just increasing the icon sizes and font sizes in whatever apps you may be using? That way things would be of a readable size while also not having the overhead of HiDPI scaling
In terms of the interface, I suppose it would depend on the application and how a person used it. If a person interacted with it solely through text and keyboard shortcuts there's no need to even bother with its GUI elements and menus on a meaningful level. On the other hand, if many elements of the app can't be resized, or the app doesn't have great keyboard shortcut support (even of you can create keyboard shortcuts for the menus there may be nothing you can do with other interface elements, such as GUI menus in photography and image editing apps) you're only solving part of the problem.
If the computer can be set up to perform specific tasks comfortably, though, say for someone who uses it for a specific line of work, that might work well.
I just wonder about the whole exercise, though. Sure, someone can go through all that trouble to make individual applications usable at such an absurdly high resolution (relative to screen size) but ultimately they won't be as usable as the app would be at a size more compatible with our senses. And what's the benefit? Fitting more on the screen at once? I think a very good argument could be made that navigating between applications and content with a keyboard is significantly faster than using a mouse, and one can use a keyboard in OS X to jump between screen-monopolizing applications and separate spaces with incredible speed and efficiency if only they familiarize themselves with the involved features and processes.
It was a learning experience for me when I went from using my cinema display to my mobile (recently sold) 13" MBP. I had to reimagine how I used my computer because I simply couldn't get things done in the way I once had on my massive monitor. But I learned and became familiar with it, and oddly now, back on my Mac Pro, I have absolutely no desire to manage my window sizes so I can tile different things on my screen. It's just so much easier to use the window management features in OS X.
The only other consideration that comes to mind with using a third-party app to run the RMBP at native resolution would be whether it still carries out that screen-doubling-downzising routine. If so, that could have a legitimate impact on performance as well (even if small, it's another thing that adds up over time). But that should actually be a non-issue if that process is abandoned.
