For apps that backup to the cloud like gmail, contacts, calendar, astrid, evernote, etc i do nothing.
For documents and pictures i use dropsync and dropbox to automatically sync photos and documents to the cloud and my pc running dropbox.
For apps that dont sync to the cloud but have meaningful data (like games) and also for system settings like my text messages, call logs, bluetooth pairings, homescreen configurations, etc i use TitaniumBackup and let it backup on a schedule. I dont backuo all apps since they come back from the market after a wipe. I just backup the ones with data that matters to me. I also sync my TitaniumBackup folder to my dropbox using dropsync so that my backups are instantly in the cloud and on my desktop and laptop. I do the same with my clockworkmod backup directory.
I like the dropbox because it keeps things not only in the cloud, which is nice, but also on my pc since i have dropbox on there and sync is automatic on it. Basically all my files that matter make it to my pc instantly without ever having to connect a cable. From there i can move or copy the most important ones like my nandroids for a hard backup.
I use iSyncr to sync my iTunes playlists and playcounts between my iTunes, phone, and tablet. And by sync i mean true sync so that when a playlist is updated in iTunes it gets updated on my phone.
Typing it out it all seems like a lot, but it really only took like 10 minutes to configure, and because the settings are all backed up, they are easily restored after a ROM flash or wipe.