What configuration options for MySQL provide the biggest speed improvements?

I'm wondering about actual configuration file improvements, table types, hardware setups, replication, etc. Anything other than the query structure and table structure (these are easy to find on the website and Stack Overflow). Are things like query cache settings what gave you the most speed? How about drives; is it better to have it on an external RAID or internal? Did replication give you better performance, especially with read large queries?

What other settings/changes have you made to improve the performance of MySQL?

Note: I realize these are very usage dependent (that is, small website vs data warehouse), but as I think most of us probably work on a variety of sites/systems, it's good to know a variety of techniques that can apply to different situations. Also, I think some techniques can be transferred between situations.