Assuming the following all are DDR3 with the SAME EXACT Frequency, CAS Timings, Voltage and Type including RAM IC's:
My preference is neither.
1. 3x4GB ; non Dual Channel ; if the CPU has a good IMC the difference is minimal but <1% slower.
2. 2x4GB+2x2GB ; Dual Channel no real cons
My preference if 12GB is the 'goal' is to GUARANTEE 100% Rated Compatibility, so 'I' would only purchase a MATCHED SET of 4x4GB especially if the Frequency is DDR3 1600 MHz or higher. The 4GB/stick density is so cheap per GB that I only recommend 2x4GB or 4x4GB Sets. Some 2x4GB + 2x4GB/2x2GB will NOT run at Rated speeds as I said ≥ 1600 MHz.