2x4GB is easier on the CPU's IMC and to a very small degree faster. Like looking up a number in 2 separate phone books - but doing it crazy fast. Also, 2X_GB can run at Faster Frequencies and Faster (lower) CAS Timings. The increased DIMMs often run leaner powering 4x_GB sets so to correct additional DIMM (DRAM) Voltage and/or QPI/VTT/VCCIO CPU IMC voltages often are required.