Hei Paulo - lots of questions is good.  Its starting to drive me mad (the problem that is, not your questions :-))
 
It happens even if its a new project and with just Omnisphere, nothing else anywhere.   I play my midi controllor and then in the Performance icon in X2 the yellow lines start going crazy, and the line on the left hits red and all kinds of crackling and popping follow.    
 
I tired changing the buffer size, and it makes no difference.  256, 512, 1024, same result.   

Sounds like you're maxing out one of the CPU cores.  I found this thread which offers some advice on lowering CPU taxation when running Omnisphere with multiple patches:
 
http://www.northernsounds.com/forum/showthread.php/64762-OMNISPHERE-CPU-load-reduction-Eric-any-advice
 
The thread does seem to suggest that Omnisphere will run on (just) one core, so multiple instances may be a better way to go if you can't reduce the CPU load in other ways.

"Clips and pops" sounds more like a buffer underrun than clipping. Maybe a matter of CPU load balancing? Trying to think why there'd be a difference between multiple instances versus one multi-timbral instance (which should be more efficient) and all I could come up with is that multiple instances are each going to run in their own thread. Maybe the single instance is maxxing out one core.
 
Some of Omnisphere's patches gobble up lots of RAM. Go to the System page, where there is a memory-usage meter that shows how much RAM Omnisphere is using versus how much is still available. 
 
Since you have lots of physical memory, try running it in non-streamed mode. This will cause Omnisphere to load each sample set in its entirety prior to playback, avoiding disk I/O overhead during playback. Or leave it in streaming mode but increase the pre-load memory allocation so that more of the file gets loaded before streaming starts. Also set the memory limit to "no limit".

Thanks ston and bitflipper for the input there.  The link to Spectrasonics page was quite enlightening, and its not an easy-to-find page!
Bitflipper: the System page tip you suggested wasn't on Spectrasonics list interestingly, but I will check it out and report.
 
Talking of maxing out cores ... I'm no PC expert, but does anyone know how many cores my PC has?
 

The E5-1620 has 4 cores according to the this page

A link provided by Eric himself! :^)

Update:  
Bitflipper, thanks for the tips but unfourtunately did not seem to have any affect.
 
What I discovered is that it only seems to happen on multis of a certain type: in fact those that I purchased from a certain vendor.   The multis that shipped with Omnisphere and other multis I made myself are not affected.  I contacted the vendor about this and they said that is was not unusual when playing 8 large Omnisphere patches simultaneously.   They said they should work on "powerful computers".   I really thought that I HAD got a powerful computer.   Does my computer specs not look enough?   I can easily add another 8GB RAM if it would make a difference.  I thought my PC was pretty powerful already though.    

I don't think adding more RAM will solve the problem.  It's a CPU core maxing out its processing capability.  Yours is more or less equivalent to an i7 running at a similar speed, so it's pretty damn good.  Try splitting the patches you want to play across two instances of Omnisphere, does that solve the problem? 
 
It might be worth taking an in-depth look at those 3rd party patches too, to see if you can tweak them to lessen their CPU load (as per the Spectrasonic's link).

When I split the multis over 2-3 seperate instances of Omnisphere, then the clicking/popping does go away --- this loses the playability of the original multi which is a pity, particularly when I have a relatively powerful computer to start with.  For those with lower specs than mine, then its also going to be a problem --- I think the vendor should be aware of that ....
 
I havn't yet tried all the Spectrasonics tricks or edited any of the patches to make them less CPU intensive, so I'lll have a go at that too.
 
Thanks all for your help and suggestions.
 

I'm using it on a lesser machine than yours and have never seen this problem, so I'm thinking it is maybe something to do with the 3rd party patches. Being a 32bit dinosaur, I sometimes come up against RAM issues with very ambitious multi's, but even so can usually get around that by using the "lite version" of the bigger RAM munching samples .