What is the current status of web servers…Is Apache 2.x “fast enough?”
Automattic uses Lightspeed (for PHP), nginx (for static content), and Apache (for media uploads). For WordPress-generated content, all server options are approximately the same speed.
What about APC?
Automattic uses beta versions of APC, and provides a 3-5x performance increase. It’s tied closely to the PHP version, so Automattic recently switched from PHP 4 to PHP 5.
Databases?
MySQL scales well and is easy enough to use that there’s little reason to consider other DBs for WordPress content. Other applications may have different needs. Note: FriendFeed uses MySQL to store schema-less data. Single-table key lookups in MySQL are faster than getting the data from Memcached.
Caching?
Automattic uses Batcache for full-page caching (.002 to .003 second), Memcached persistent object cache, very limited MySQL query cache (never larger than 256MB), sufficiently large key buffer.
HyperDB?
HyperDB solves DB scaling problems.
Backups
User-data backed up every hour, if something changed. Every blog backed up every 12 hours. Dedicated MySQL slaves do LVM snapshots for backups.