Tuning APC (Alternative PHP Cache) to work with Drupal is a relatively painless process. As Dries Buytaert has noted, APC can help serve Drupal pages up to 4 times faster than a stock Apache and PHP setup.

However, tuning APC for use with more than one Drupal instance can be a little bit more challenging than a single site running on it's own server.

For example, on one Drupal 5.x site developed by Openject, APC is installed and running on a server with 8GB of memory and a large MaxClients and lowish KeepAliveTimeout (5 seconds). The server is setup for a single Drupal site and performs best with an apc.shm size of a mere 64mb, or 0.78% of the total memory available on the server. In fact, 64mb is more than the site needs as shown by this APC graph:

On another server with only 2GB of memory also administered by Openject, APC is installed and configured to work with more than 5 Drupal sites (including some multisite instances). In that case, an apc.shm size of 64mb (or more) is required over the default 32mb because APC would fill the cache every 5-10 minutes and flush itself, decreasing performance (check the "Cache full count" section in apc.php--less is better).

The tricky part about APC with multiple Drupal sites on a single server is determining what is a good value for apc.shm without causing too many cache flushes, while at the same time minimizing the amount of resources devoted to APC. While 96mb or even 128mb could be beneficial to the aforementioned server, there are other services running (and some other Python based sites) that also require memory of their own.

In the end then, there is no tested formula or best configuration to use with APC and PHP. It requires a little bit of trial and error for an Apache+PHP+APC server to hone a configuration to that specific server and the Drupal site or sites hosted on it. However, the effort involved is minimal and as such, it is well worth spending the time configuring APC for the performance gains it will provide in the long term.