My PC (see specs) originally had 16GB DDR3 as a 4x4 arrangement. For years it was intermittently unstable, ie BSOD and other niggly errors. Really intermittent, so much so that troubleshooting just couldn't pinpoint it, including removing the memory modules. It often looked like software was doing it, but I didn't think so.
A couple of years ago, the instability started to get noticeably worse where it would BSOD every few minutes which allowed me to finally track it down to one of the memory modules with 100% certainty. I did notice that with 4 modules installed, they were all running hot, with the one closest to the CPU very hot, even though the PC isn't overclocked. I suspect that this heat was enough to make the module unstable and eventually to damage it, or maybe it was slightly faulty from new, I'll never know. I don't know if that faulty module was actually in that slot though.
I then replaced all the modules with new 2x8 Corsair modules of the same type and model range and put them in slots 1 & 3 so that the closest slot isn't occupied and the PC has run fine ever since - a blessed relief after all that time not running quite right. The two modules run a lot cooler, too. I've actually got another 2x8 modules used bought from a friend as part of a spare mobo / CPU / RAM / cooler bundle. I tried them and while it was great seeing 32GB in this old Sandy Bridge rig, the modules ran hot again, so I've removed them. I don't need 32GB and it's just not worth the headache. I'd have to add an extra fan there to fix the heat problem and that's not good for a PC built to be very quiet.