I've done it. It is not as bad as it looks. Though you need to very careful with the connectors, especially the large flat LCD connector. There are quite a few people who have damaged that one. It is very easy to shear it off the motherboard if you apply to much pressure when re-mating it, I did on my 2009 iMac. I was able to solder it back on, hadn't used my soldering iron since college. Luckily it didn't damage the pads and came off cleanly.
I've also run externally connected drives that are connected all the time without issue.
In my opinion if your going through the trouble of opening up your iMac, I'd go ahead and upgrade it to all SSD storage internally than use nice raid style enclosure externally. That way failure prone Hard Drives are easy to access, and can be protected via raid, and it is easy to upgrade as your storage needs increase.
It is cheaper than you might think with the drop in SSD prices, and OWC Thunderbays are pretty reasonable.