I've decided that I'm not going to sync my iOS devices to iTunes any longer. This is not due to being unhappy with iTunes (I actually don't mind it), but it's about reclaiming 28 GB of hard drive space. In a world where the low end 13" MacBook Air comes with a 128GB drive, this is about saving space. Apps were taking up 4 GB and music was the other 24 GB. Here is how I am managing media/content without iTunes:
Apple stores my purchases from the cloud, so there is simply no reason to keep them. With the growth of retina optimized apps, they are not getting smaller in file size.
I am using iTunes Match on iOS and Apple TV, so why not on the Mac? I've removed all the local files, but I can still play music through iTunes Match. I'm rarely using my Mac when I don't have a WiFi connection, so the lack of offline copies doesn't matter to me. You can accomplish this by deleting all your music (CMD + A and hit the delete key). The next dialog box after deletion will confirm your choice. You also want to make sure the 'Remove from iCloud' is unchecked. You can redownload songs at anytime as well.
I never listen to podcasts on my Mac, so by using Pocket Casts, I can managae them on iOS.
I buy the majority of my books from Audible, but I do buy some DRM free ones from other places on occasion. It's easy to download Audible books as it allows OTA (over the air) downloads and their app is actually really good (it used to be terrible). For the moment, I am doing 'Open In' from Dropbox to Downcast for audiobooks that I purchase outside of Audible. It's not perfect, but it allows me to adjust playback speed and it remembers playback position. Ideally, I'd like to see Audible allow me to import books to its app.
iTunes purchases/rentals are downloaded OTA. Non iTunes media is handled by Plex and the Plex iOS app. I wrote up the details of this solution a few months back. If you want to store Plex content offline on your iOS device, I would definitely look at subscribing to PlexPass. They have monthly, yearly, and lifetimes options. I don't need to often, so I just subscibe on the months when we have travel plans.
I've used iCloud backup and restore with each new iOS device I've bought since it was added. It's worked flawlessly everytime, so I feel secure relying on it as my only backup. Even if I didn't have a backup, the majority of my data is held with other cloud services (Evernote, Dropbox, etc).