Do you want 2 x 4 gigabyte and 2 x 8 gigabyte sticks or 2 x 4 gigabyte and 1 x 8 gigabyte?
Both may work with the right board/cpu/os support.
Now running an uneven number if sticks can lead to the system falling into single channel memory mode. This can have a performance impact for sure. In the best case your board would run the first 8 gigabytes with dual channel and the last as a single if you had 3 sticks. This is a flex mode offered on many boards.It is not perfect, but works.
You also have to look into compatibility issues, no all boards or operating systems will allow extra ram(over 16 gigabytes for Windows 7 Home Premium). In rare cases a system will simply not like sticks that are not sold in sets. I have only seen it 2 times, but it DOES happen. In this case it could be a simple fix with more voltage or looser timings/slower speeds, but in other cases it will simply refuse to get along.
Most boards have a list of tested memory and it is generally recommended to get sticks in pairs for system you are using and a set of 4 if you want to fill all slots. I have had very good luck mix and matching memory, but it just takes on time of it not working to leave you with memory you have no other use for.