We've been using Backbone+Marionette at my company, and in general I like it, and it's much cleaner than just vanilla Backbone, but I still feel like it falls short for medium-to-large sized apps, and requires you to write a substantial amount of additional code, or include additional Backbone plugins. This might include things like "nested/deep" model support, two-way data-binding, etc. The main problem with the lightweight plugin model is that a lot of the plugins aren't necessarily compatible with others, or are not up-to-date on the latest Backbone changes, not to mention the varying degree in quality and maintenance of plugins, and the problem of choosing which data binding plugin you want, out of the 10+ available.

I think maybe we have just crossed the line from small, focused UI/interactions to large-scale single-page apps, and we would be better off with a more substantial/fully-featured framework like AngularJS or Ember.js.