This question was asked in 2011 and Django has come a long way since then. I've previously build a social network with 2 million users on Django and found the process to be quite smooth. Part of getstream.io's infrastructure also runs on Django and we've been quite happy with it. Here are some tips for getting most out of your Django installation. It wasn't quite clear from the question but I'll assume your starting from a completely unoptimized Django installation.
Static files & CDN
Start by hosting your static files on S3 and stick the Cloudfront CDN in front of it. Hosting static files from your Django instance is a terrible idea, please don't do it.
Database & ORM: Select related
The 2nd most common mistake is not optimizing your usage of the ORM. You'll want to have a look at the documentation regarding select related and apply it as needed. Most pages on your site should only take 2-3 queries and not N queries as you'll typically see if you don't use select related correctly:
https://docs.djangoproject.com/en/1.11/ref/models/querysets/
Database: PGBouncer
Creating a new connection to your postgres database is a rather heavy operation. You'll want to run PGBouncer on localhost to ensure you don't have any unneeded overhead when creating database connections. This was more urgent with older versions of Django, but in general is still a good idea.
Basic Monitoring & Debugging
Next you'll want to get some basic monitoring and debugging up and running. The django debug toolbar is your first friend:
https://github.com/jazzband/django-debug-toolbar
After that you'll want to have a look at tools such as NewRelic, Datadog, Sentry and StatsD/Graphite to get you more insights.
Separate concerns
Another first step is separating out concerns. You'll want to run your database on its own server, your search server on it's own server, web on their own servers etc. If you run everything on one machine it's hard to see what's causing your app to break. Servers are cheap, split stuff up.
Load balancer
If you've never used a load balancer before, start here:
https://aws.amazon.com/elasticloadbalancing/
Use the right tools
If you're doing tag clouds, tag search or search use a dedicated tool such as Elastic for this.
If you have a counter that is frequently changing or a list that is rapidly changing use Redis instead of your database to cache the latest version
Celery and RabbitMQ
Use a task queue to do anything that doesn't need to be done right now in the background. The most widely used task queue is Celery:
http://www.celeryproject.org/
Denormalize everything
You don't want to compute counts such as likes and comments on reads. Simple update the like and comment count every time someone adds a new like or comment. This makes the write operation heavier, but the read lighter. Since you'll probably have a lot of reads and very few writes, that's exactly what you want.
News feeds and activity streams
If you're building feeds have a look at this service for building news feeds & activity streams or the open source Stream-Framework
In 2011 you had to build your own feed technology, nowadays this is no longer the case. Build a social network with PHP
Now that we've gone over the basics lets review some more advanced tips.
CDN and 2 stage loading
You are already using Cloudfront for your static files. As a next step you'll want to stick Cloudfront in front of your web traffic as well. This allows you to cache certain pages on the CDN and reduce the load on your servers.
You can even cache pages for logged in users on the CDN. Simply use Javascript to load in all the page customizations and user specific details after the page is served from the CDN.
Database: PGBadger
Tools such as PGBadger give you great insights into what your database is actually doing. You'll want to run daily reports on part of your log data.
Database: Indexes
You'll want to start reading up on database indexes. Most early scaling problems can be fixed by applying the right index and optimizing your database a little bit. If you get your indexes right you'll be doing better than most people. There is a lot more room for database optimization and these books by the 2nd quadrant folks are awesome. https://www.2ndquadrant.com/en/books/
Database: Tuning
If you're not using RDS you'll want to run a quick PGTune check on your database. By default postgres' configuration is pretty sluggish, PGTune tells you the right settings to use:
https://github.com/gregs1104/pgtune
Cache everything
Scaling your database is a pain. Eventually you'll get around to having multiple slave databases, handling sharding and partitioning etc. Scaling your database is time consuming and your best way to avoid spending tons of time on that is caching. Redis is your go to cache nowadays, but memcached is also a decent option. Basically you'll want to cache everything. A page shows a list of posts: Read from Redis, Looking up user profiles? Read from Redis. You want to use your database as little as possible and put most of the load on your cache layer since it's extremely simple to scale your cache layer
Offsets
Postgres doesn't like large offsets. Use ID filtering when you're paginating through large result sets.
Deadlocks
With a lot of traffic you'll eventually get deadlocks. This happens when multiple transactions on postgress try to lock a piece of information and A waits for B while B waits for C and C waits for A. The obvious solution is to use smaller transactions. That reduces the chance for deadlocks to occur. Next, you'll want to batch updates to your most popular data. IE. Instead of updating counts whenever someone likes a post, you'll want store a list like changes and sync that to the count every 5 minutes or so.
Those are some of the basic tips, have fun dealing with rapidly growing social networks :)
