Depends on what your motherboard supports. Some motherboards support quad channel memory, most support dual channel, and some older ones support triple channel. I'd expect your board supports dual channel, so yes, 8gb x 2 is the best option. If you want an exact answer, post what motherboard you are using.
To answer the OPs question, fewer is better. 2x8 is better than 4x4, less stress on the memory controller and easier to determine faulty memory if problems arise. I do concur with Swordkd that it does depend on the motherboard. Most of the earlier motherboards based off the Intel 5-Series (P55/H55) don't support DIMMs larger than 4GB.
Should I use 4 sticks of 4gb totalling 16gb or 2 sticks of 8gb totalling 16gb?
As mentioned in the earlier post the motherboard model number will really help. Each motherboard has its own memory limitations and memory population rules.
#. Firstly, make sure your motherboard supports 16GB or more memory. If it is true then make sure your motherboard has more than 2 slots. If that is also true, then you can consider if you are to install a two 8GB or 4 4GB.
As mentioned in some of the post, even I do agree that going with two 8GB is the better option rather 4 4GB modules (and that's a strong Yes, if you have an AMD CPU). Also this might leave you with the free slots and you can utilize the same when you upgrading the memory in the future instead of ditching the 4GB modules. Hope that helps.
but also want to keep in mind, for the purposes of this guide, the testing was with 2 and 4GB sticks not 8GB big boys, and also they just group the figures by family i.e. they show 2 sticks of 1866 for FX CPUs - though in reality the 8350 and 8150 are about the only two that can be relied on to run 2 sticks of 1866, a fair percentage of 8120 and 8320 can run 2 at 1866 but the bulk have trouble - etc