I went the other direction... I started out with a full-blown HTPC in my main Theater about two years ago. I spent a few evenings setting everything up, mainly tweaking the interface and optimizing my network layout, but it all came together pretty easily. After the initial setup, things churned along mostly unchanged for nearly 2 years (was still running 9.11 up until about 2 weeks ago).
Then, after reading an Engadget article about XBMC on the ATV2, I decided to add them as clients for secondary screens (Master Bedroom, Kids' Room, etc). I had a Revo AR3610 in the Master Bedroom, so I sold that and made enough to buy two ATV2s and a new router with built-in USB NAS. This re-sparked my interest in XBMC and has lead to far more learning and tweaking than I ever did with my old basic setup.
The main thing I found when setting up multiple clients was the need for a unified UI. The ATV2's horizontal Confluence was different than the vertical Confluence on the HTPC in the theater (9.11) and the P4 I had recently cobbled together for use in the Living Room (10.1). This lead me to updating both HTPCs to nightly builds so the UI would be uniform on all screens.
The next consideration for multiple clients is synchronization. The first step has been moving away from letting each XBMC client do its own scraping and instead using a central scraper (Ember in my case) that generates NFOs, Coverart, Fanart, metadata, etc and stores it in the same folder as the media itself. This required an update to my folder structure since, up until this point, I had simply piled individual movie files into a "Movies" folder. Luckily Ember was able to automate the process. Now that scraping is done centrally and NFOs/Artwork are stored with the media, each client pulls them directly and everything remains in sync.
The next step will be setting up a MySQL server to allow synchronization of WATCHED tags and RESUME function. Being able to pause in the Theater or Living Room and pick back up instantly from the same location in the Master Bedroom will be a boon. It shouldn't be too difficult to setup, I just need to find an evening or weekend afternoon that I'm not already committed to another project AND my wife is out of the house (i.e. not bugging me to do something for her every 15 minutes or bitching when I need to temporarily commandeer her TV for setup/testing).
Lastly, managing add-ons has become the most manual process of multi-client administration. To date I've been manually installing the necessary REPOs on each client and then manually installing the add-ons themselves, changing settings when required, and organizing home screen shortcuts for consistency across each client. In the future I may look into administering add-ons by installing on one machine then copying the installed add-ons folder out to the other machines.
Once the MySQL server is up and running, I'm predicting that occasionally watching for new add-ons will become the extent of my XBMC tweaking. At that point I'll have achieved my main functionality goals and won't have much reason to spend time continually tweaking/upgrading/etc. Maybe then I'll learn Python
As for the HTPC that I started out with in the Theater (an Acer Aspire AX1301-9052), my plan all along was to toss in a Blu-Ray drive and setup TMT5 as an external player for BD discs. That said, over the past 2 years I've watched a grand total of 5 Blu-Ray discs and I already have a decent stand-alone BD player, so that project has continually slipped lower and lower down my priority list. It's so low now that, at this point, I'm even considering replacing it with ATV2 as well... or maybe ATV3 if it's A5 powered. I would not have a problem with every XBMC client in the house eventually being an ATV device.
