Having multiple Macs as part of your day to day life is a little more tricky than I would like, but I manage. For the most part, my iMac has the most up to date copy of everything I have or do, while my MacBook Air has only the most basic collection of files. Mail and calendar items, iTunes music and shows, etc all stay on the iMac alone. Everything I need gets synced with my iPhone, which is more handy anyway, so it isn't a hassle. I try to keep the MacBook as trim as possible, but that takes discipline. Back when I had a PowerBook, things were reversed (I had the PowerBook before the iMac), with all my calendar and email on the laptop. When the iTunes library got unwieldy, I moved it to an external drive (which I still use, only now attached to my AirPort network). What helped me most, as strange as it may sound, was getting an Eee PC as a transition from the aging PowerBook to my new MacBook. I spent about two months on the little Linux box, surviving with just an 8GB SD card to hold all my day to day files. It wasn't the most comfortable arrangement, and I was very, very happy to come back to a Mac, but it taught me a lot about what files I really need on a daily basis. The most surprising thing was that after the initial shock that not everything would fit, I hardly ever maxed out the 8GB card! Now with the 80GB drive in the MacBook, some of that discipline is lost, but I've still got 40GB free.
The core of what I've done is to eliminate loose files in any of the main folders in my User directory (Documents, Pictures, Movies, Music, Sites). On my iMac, I've got 83 folders in my Documents, 19 of which are mirrored on my laptop. Since I use the laptop at school, and all my music is already on my iPod/iPhone I don't keep any music on the laptop (or any photos in iPhoto). I have a web collection of photos as well as some selections on my iPhone, so no trouble there (what I do have on the laptop mainly consists of desktop background images and photos I need for school). The Movies folder is also pretty sparse on the laptop, mostly consisting of a few YouTube videos I found funny or a movie trailer or two. Whenever I remember I just move these files back to the iMac and delete them from the laptop. I do keep my Safari bookmarks synced, but only by using the most arcane method of "Export Bookmarks..." that is built into Safari.
As for keeping what few user documents and files I have in sync with the home iMac, I basically use the Shared drive feature right in the Finder. I keep a few folders duplicated on both systems, so I can just drag and drop from one to the other and overwrite without fear. Time Machine is keeping track of things in the background too, so that helps as well. I've tried a lot of other Sync apps, but none really "clicked" with how I work on my machines. To each his own, I guess.
As far as everything else, eh... it's not that big of a deal if it's out of sync since they're both being backed up via Time Machine