Akin to this question, "I'm looking for the pros and cons of each framework and why one is particularly useful over the other" (but mostly what Flatiron has to offer, due to the fact that Express is already detailed pretty well in that question).
From my slight experience with Express, it seems to cover just about what you need and no more. Flatiron seems to do that, but much more minimalistically. If you check their website, you see that they offer around 5-7 main functionalities, compared to the many others included in Express.
Finally, which seems the most promising for a highly-scalable web app(s), and why should I use this or that framework over not using a framework at all?
Some update after a year and a half after this question was asked:
The first difference that comes to mind when comparing Express to Flatiron is that Express is a server-side framework while Flatiron is advertised as being isomorphic, covering both the server side and the client side and as such should be suitable to develop traditional server-side applications, client-side single-page application and everything in between (much like eg. Derby or Meteor). However, I have failed to find any examples of client-side usage of Flatiron, and not for the lack of trying.
There is an issue on GitHub to provide a simple TODO app example that's been open for over two years and (from what I understand reading the comments there) you cannot build a client-side app using Flatiron alone, without adding things like jQuery, Backbone etc. because the client-side aspect of Flatiron doesn't seem to be ready yet ("We are working on it. We still have a few more steps to go to make it completely isomorphic.") which seems like a real problem for a framework that tried to be isomorphic from the start. (See also a related TodoMVC issue: Add FlatIron example).
The conclusion is that Flatiron is not ready yet. When it is ready it may cover much more areas of Web development than Express does, but it's really hard to tell when it might be, if a simple TODO app example couldn't have been provided for years.
Meanwhile there are tons of Node frameworks and it's really hard to keep track of them so what I'd recommend doing now and in the future would be to see the list of Web frameworks on the Joyent/Node wiki on GitHub and compare them to the client-side frameworks on the TodoMVC project - where those both lists intersect would be frameworks that cover both the server and the client and are capable of writing a simple TODO app in them - which hopefully will include Flatiron one day.