I had this issue too, it was down to the network interfaces. There are a few tools you can run to isolate where the bottlenecks are… read this thread… A must-watch for users with real-time issues! - Cubase - Steinberg Forums , some of those tools are mentioned. For me, the built in Ethernet interface was the issue. all pops and crackles stopped when I disabled the interface. Most folks these days want to surf the net on their DAW, I have other machines for that, but it did bother me when I wanted to download patches, and so on, to hear that stuff. I bought a USB Ethernet adapter, left the internal one disabled, and now I can leave networking enabled, and no more noise in playback. Same goes for some Wifi setups.
Good luck.