My partner and I built a non-trivial web site on Django. When the next version ships, there might not be a single Django module imported.
We're not trying to drop Django; it is just sort of happening. Piece by piece, it is failing to meet our needs. Despite the marketing copy on the Django site, most components of the framework are tightly coupled enough to make customization frustrating. It is often easier to rewrite core framework components than to implement them on top of the existing extensibility points.
What follows is a loose chronology of our migration away from Django.
URL Routing
A flat list of patterns violates the DRY principal when creating nested URLs. Trees are a superior representation. Having a tree of views also enabled us to optionally associate a "binder" function with each node. These bind functions are executed for each URL component from left to right, filling the template context as they go. Breadcrumbs are automatically generated as each node binds, but only the last node executes its full view logic.
Authorization
Our site enforces permissions on every resource, but Django's database ACLs would have been prohibitively numerous. Instead, views or their URL binders may raise an AccessDenied exception. Upon catching such an exception, a middleware layer serves a login form. This ensures users have permission to access the current resource, as well as all ancestor resources bound to the URL.
Authentication
Both of Django authentication's key extensibility points are flawed. These two extensibility points are "user profiles" (storing additional per-user data) and custom credentials (such as for logging in via email address instead of username). Django's documentation and numerous internet sources cover both topics, but all of the guidance lacks important caveats. The admin UI, in particular, is very easy to break with either extensibility mechanism.
Extending the User model with the ORM requires a one-to-one database relationship. This relationship can be implemented with a "user profile" setting, an explicit foreign key, or model inheritance. Each approach has its own strengths and weaknesses in terms of performance, API semantics, subtle behavioral changes, and outright bugs.
Enabling custom credentials requires implementing a trivial authorization "backend" object. Unfortunately, it is non-trivial to replace usernames with email addresses. The admin UI's login form refuses to accept email addresses without hacking the template. Even if you hacked the template, the User model would still enforce a non-null constraint on the username field and the generated database schema enforces a uniqueness constraint as well. It turns out to be easier to fill the username field with a dummy value and "support" both forms of authentication with your backend, but you won't come to that conclusion until your head has already bore a hole in your desk.
Templating
We do our best to keep view and template logic separate. Django's templates are targeted at designers, who aren't implementing any real logic anyway. However, we're a pair of hackers. Sometimes it is just more convenient to put a little bit of logic in the views. Besides, templates are code; code needs to be reviewed and tested. We wouldn't ever hire a designer who couldn't pass a code review for some trivial template logic.
We needed a pragmatic template language to replace Django's idealistic one. Any template language with greater expressive power would have been welcome, but Jinja2 fit the requirements and provided the easiest migration path. Ultimately, we'd prefer to use something like HAML, but there doesn't seem to be a Python equivalent besides the inactive GHRML project. We are, however, using SASS. I will never write CSS by hand again.
ORM and Admin UI
One of Django's most touted features is the Admin UI. For simple "active record" style database models, the Admin UI is a huge time saver. Sadly, it struggles a little bit with nullable fields and is tricky to customize. You'll definitely need to write custom UI for complex models, but by and large the admin solves the problem at hand: viewing, creating, updating, and deleting database rows.
After using the Admin for a little, I found myself missing Microsoft Access. I never thought I'd say that, but it is true. Django's admin does not support sorting, filtering, or other impromptu queries. Edit: It turn's out I was mistaken about sorting and filtering, but I stand by the core message of this section. I found myself writing impromptu queries in the database and Python shells. After a while, I just gave up and installed a desktop client. I haven't visited the Admin UI since.
Django's ORM has shortcomings with respect to querying, especially for joins and aggregation. It has been improving over time, but it will likely never reach the capability of projects solely focused on databases, such as SqlAlchemy. With the admin having fallen into disuse, the Django ORM lost all advantage. Beyond Django's specific weaknesses, I've come to believe that the schema-generative ORMs paradigm is fundamentally flawed. That is a topic that deserves an entire (Django-agnostic) post of it's own. We are now using SqlAlchemy via schema reflection; no declarative layer.
Form Validation and Generation
Here is where our chronology meets present day. We are still using Django form validation, but never used form generation beyond scaffolding. Nearly all of our templates customize labels and display of errors. Additionally, embedding widget information in the Python code is cumbersome during template development. Django forms is a quality validation library, but there are some inconsequential style things that I like better about FormEncode. Preferences aside, the difference isn't large enough to justify switching.
While I like FormEncode, I'm still not sold on its anti-form-generation companion, htmlfill. I think there is a middle ground with form generation that provides scaffolding during development, smoothly transitions to production use, and cooperates with validation. As we implement more complex client views, I'll be on the lookout for ways to improve our form development toolbox.
So, ugh... What's left?
Besides a few isolated helper functions, not much is left of Django.
The last big ticket item is the HTTP framework and WSGI server. We could continue using Django as if it were CherryPy or Paste, but Django has this nasty habbit of insisting on running your code for you. The settings and manage.py infrastructure are fiddly for deployment and don't really add any value over simple scripts using our application like a library. Might as well use a simpler WSGI library, and replace those over-engineered management/commands/foo.py files with vanilla scripts/foo.py files.
Moral of the Story
I'm sure there are numerous lessons to be generalized from this journey. Personally, I've developed a moderate fear of the word "framework", as well as altered the way I think about software abstractions. I think the most important lesson, however, is one I already knew: choose the right tool for the job. Unfortunately, we had no idea what the right tool was when we started. I'm not sure we know any better now.