Overhead of a Round-trip to MySql?
Just because you are using an ORM doesn't mean that you shouldn't do performance tuning. 
I had - like you - a home page of one of my applications that had low performance. I saw that I was doing hundreds of queries to display that page. I went looking at my code and realized that with some careful use of select_related() my queries would bring more of the data I needed - I went from hundreds of queries to tens.
You can also run a SQL profiler and see if there aren't indices that would help your most common queries - you know, standard database stuff.
Caching is also your friend, I would think. If a lot of a page is not changing, do you need to query the database every single time?
If all else fails, remember: the ORM is great, and yes - you should try to use it because it is the Django philosophy; but you are not married to it.
If you really have a usecase where studying and tuning the ORM navigation didn't help, if you are sure that you could do it much better with a standard query: use raw sql for that case.
So I've been building django applications for a while now, and drinking the cool-aid and all: only using the ORM and never writing custom SQL.
The main page of the site (the primary interface where users will spend 80% - 90% of their time) was getting slow once you have a large amount of user specific content (ie photos, friends, other data, etc)
So I popped in the sql logger (was pre-installed with pinax, I just enabled it in the settings) and imagine my surprise when it reported over 500 database queries!! With hand coded sql I hardly ever ran more than 50 on the most complex pages.
In hindsight it's not all together surprising, but it seems that this can't be good.
...even if only a dozen or so of the queries take 1ms+
So I'm wondering, how much overhead is there on a round trip to mysql? django and mysql are running on the same server so there shouldn't be any networking related overhead.