Anytime you exceed about 32 "loads" on the bus, the signal deterioration is fairly severe from an electrical perspective. You can compensate somewhat with higher voltages; longer timings; and/or slower speed ... and if you're lucky the memory will work okay. But it is NOT reliable enough for "mission-critical" use -- that's why server boards use registered or FBDIMM modules ... with buffered modules there's one load per module instead of one load per chip (with double-sided ECC modules that's 1/18th the load of unbuffered memory !!).
Personally, I never exceed two double-sided modules in an unbuffered board -- I like rock-solid performance in my systems. A LOT of "glitches" folks notice in their systems are simply memory errors caused by unreliable memory subsystems -- especially when they install 4 modules in an unbuffered board.
What would you "notice??" Probably just occasional crashes that you'd likely attribute to Windows ... but which most likely wouldn't occur with only two modules.
