defragging
Macs do slow down about every 6 months or so as well in my experience - not an exclusive PC problem.
The thing I've found to make the biggest difference, both in terms of startup speed and general operating speed is defragging.
I know there's some controversy about this, with many saying "but Macs defrag themselves automatically", and maybe to some extent they do, but after buying and running iDefrag I've seen it for myself. iDefrag shows you the level of fragmentation on your HD (showing nice scary red bits where there's supposed to be fragmentation), and you may say that iDefrag would be biased to try to show you that there's lots of fragmentation even if there isn't (after all it would be trying to justify it's existence), but I really did notice the difference. Startup was somewhat faster (I'd guess probably because the various OS updates over time must also make a bit of a mess of where on the HD your operation system is actually installed), but mostly things like starting up iPhoto was noticeably faster.
In addition I regularly run Snow Leopard Cache Cleaner for general maintenance (like repairing permissions).