Are you using Omnisphere in multi-mode? I was never sure whether it was better to run it in multi, or just insert a new instance for each patch with a single stereo out - and I read somewhere that the latter approach can produce less demand on the processor (somewhat counter-intuitively).
My setup is similar(ish) to yours in the CPU department and I can normally have 5 or so instances of Omnisphere plus Kontakt, Arturia synths, audio tracks as well as numerous plugs without breakups.
<EDIT> I'm not on the latest SPLAT release btw (Manchester I think). Also, I don't disable anti-virus or any other services because it is always connected, and when I get bored I need to quickly jump into Elite:Dangerous!