Let me give you some example:
1. Large file transfer, say 50GB single file from another PC from the same network , lets say a NAS to my main PC will make the whole system laggy and not responsive. Yes , even in Safe Mode with networking. I reinstalled my Intel I-218V LAN adaptor , not helping neither. I increase the interrupt moderation rate on the LAN adaptor, not helpful.
2. I'm running on Unifi ISP with 500mbps DL and 100mbps UL. When I run speedtest.net with latest 64bit Chrome browser with adblock plus + Tampermonkey anti adblocker add-in, my system will become unresponsive and lag. Getting only like 460Mbps DL and surprisingly still getting 100+mbps UL . I went to Safe Mode, I did the same test , at last getting 500mbps DL 100mbps UL.
There is a common symptom when I did both test . In task manager, 1 of the CPU Core Utilization goes up to 100% , that is where the computer becomes unresponsive.
What I did after that, disable HTTP scanning protocol on my anti virus ( I'm running on the latest ESET NOD32 AV), turn off windows defender firewall . Not much better still.
Next thing I did, I disabled my Spectre vulnerability patch and reboot my machine. Walla , all my unresponsive issues gone altogether and even browsing internet is more responsive than before. Redo speedtest.net, i'm getting reduced latency and better DL and UL speed.

My current rig spec:
Win 10 version 1803
Core i5 4690k running at 4.5ghz core , 4.3ghz uncore
16GB DDR 3 2400Mhz on dual channel
256GB Samsung PM961 NVME SSD ( an enterprise variant of the Samsung 960 Evo)
My NAS (home build):
Win 2008 R2
Core 2 Quad 9650 running 3.6Ghz
8GB DDR2 800Mhz RAM
4TB of HDD storage ( 1TB X 4 running on RAID 0)
Both of them on gigabit network. Router TP-Link Archer C9 .
Sep 1 2018, 04:23 PM, updated 8y ago
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