Some useful suggestions in this thread; worth reading.
This is something I just started thinking through in earnest after getting a new i7 iMac and a Touch; I'd been pretty much using my MBP by default for the last couple of years because I'd been too lazy to come up with a synchronization system, but frankly there are good reasons to want a big IPS screen and quad core machine in front of me some of the time, and to be kicked back on the couch at other times (and something in my pocket still others).
My file solution is simple; I have a mini with external drive running as a combination file server/HTPC, and just work directly off the network on it. Big media files are slow over wireless, but everything else is smooth and even iPhoto has no issues via gigabit ethernet, so that's worked fine. Doesn't do me any good away from home, but frankly I don't do that much computing elsewhere.
Media is the same; iPhoto libraries, fansubbed videos, and iTunes library all go on the mini, and are accessed via the network if needed. The other computers also do Time Machine backups over the network to the server, which is nice.
Address Book synching through Google is a bit funky, but seems basically functional (and has the added bonus of your address book being available via gmail's web interface). Free, too, which is an advantage over MobileMe.
Email I settled on a "main" machine using POP to grab stuff routed through gmail to store local copies, and using IMAP from the Touch and desktop to get to archives the rest of the time. (I just have never been able to bring myself to trust IMAP completely, and my work email doesn't provide nearly enough storage for IMAP to work long-term, but this seems to work well enough.) Now I just need to figure out how to get my Touch to let me pick from multiple "from" addresses.
Bookmarks for me have ended up being the sticking point; I use Camino, Safari, and Firefox all simultaneously for different purposes, and with different bookmarks in each (Firefox for certain online games that run best in it, Safari for general purpose, Camino for media playing and some foreign-language stuff, so I can default it to a different character set for badly-coded sites). Maybe weird, but it works for me. Problem is, I want to synch my bookmarks for all three browsers between desktop and laptop, but I do NOT want to synch bookmarks from one browser to another. Not many apps claim to do this.
The app
BookMacster (replacing the older Bookdog) claims to be able to do this. I just got in on the beta, so yet to see if that ends up panning out. I sure hope so.
Synching the rest of my prefs would be nice in some cases, but not others (I want different Photoshop settings on my beefy desktop than my older MBP, for example), and desktop/Downloads folder/Documents folder don't seem as important--I figure if anything is really important, I'll put it on the server anyway.
I should probably just bite the MobileMe bullet, but I just can't bring myself to spend that much for a service I'd mostly be using to synch my address book.