Can I use only two 8 GB RAM modules with my mid 2010 27" iMac (2.8 GHz Core I5)? In other words, do you have to fill all 4 memory slots or are 2 filled slots sufficient?
Short answer to your question is YES.
But why would you limit the memory given the price of modules today?
According to Everymac.com, your "official" max is 16GB, however you can go all the way up to 32GB. I personally used Crucial memory modules in my iMac and MacBook Pro with no problems
I would go with 2 16GB kits (a "kit" being 2 8GB modules) for a total of 32 GB RAM (a total of 4 8GB RAM modules).