Many of you RMN readers using Windows use a variety of programs to stay safe from malware popups and rootkits. Aside from Never10 mentioned here recently, here are some you might not have heard of. JRT below helped me out a lot.

RogueKiller or HitmanPro 3.
HitmanPro won't actually make changes in the default unregistered program, but it will list the deletions you'd have to make manually.

SpywareBlaster 5.5
You can also add customblocking.txt to the SpywareBlaster program directory. Then in SpywareBlaster click Tools, Custom Blocking, then right-click in the ItemName/CLSID list, then choose Select All, then click Protect Against Checked Items. IF YOU DO THIS, and then run Hitman Pro, and look at the results list, you'll have to know to ignore the CLSID popups that CustomBlocking.txt added.

Malwarebytes: Junkware Removal Tool (JRT)
Winhelp2002.MVPS.org Hosts File

If you want to keep the Windows drivers updated better use Snappy Driver Installer. You can pick the 32-bit or the X64 EXE version. Running it brings up a menu to download updates of the program. Snappy Driver will add new EXE files to the location where you installed Snappy Driver (i.e. SDI_x64_R452 will download a later version, say SDI_x64_R455.exe, in the future). The first time you run Snappy Driver it might ask you to download 1.5GB of driver updates.

If you work with bootable USB sticks use Rufus.

If you're pretty adept at using about:config in Firefox, use Firefox bulls#!t removal via about:config to make Firefox more secure.

If you run all this but something still seems to be hidden in your Windows PC, certain dark souls must REALLY REALLY hate you beyond belief.

(BONUS: If you want to keep track of the sun, use ARTIS @ SolarIMG.)

If your grandparent learns how to do all this skillfully to Windows, you're probably out of a job at least with them... Which is fine by you most likely. Grandpa is not likely to ask you: how come I'm getting odd IPs popping up in WireShark?

If you really wanted to avoid a lot of Microsoft's telemetry, add this to your HOSTS file:
0.0.0.0 statsfe2.update.microsoft.com.akadns.net
0.0.0.0 fe2.update.microsoft.com.akadns.net
0.0.0.0 survey.watson.microsoft.com
0.0.0.0 watson.microsoft.com
0.0.0.0 watson.ppe.telemetry.microsoft.com
0.0.0.0 vortex.data.microsoft.com
0.0.0.0 vortex-win.data.microsoft.com
0.0.0.0 telecommand.telemetry.microsoft.com
0.0.0.0 telecommand.telemetry.microsoft.com.nsatc.net
0.0.0.0 oca.telemetry.microsoft.com
0.0.0.0 sqm.telemetry.microsoft.com
0.0.0.0 sqm.telemetry.microsoft.com.nsatc.net
0.0.0.0 watson.telemetry.microsoft.com
0.0.0.0 watson.telemetry.microsoft.com.nsatc.net
0.0.0.0 redir.metaservices.microsoft.com
0.0.0.0 choice.microsoft.com
0.0.0.0 choice.microsoft.com.nsatc.net
0.0.0.0 wes.df.telemetry.microsoft.com
0.0.0.0 services.wes.df.telemetry.microsoft.com
0.0.0.0 sqm.df.telemetry.microsoft.com
0.0.0.0 telemetry.microsoft.com
0.0.0.0 telemetry.appex.bing.net
0.0.0.0 telemetry.urs.microsoft.com
0.0.0.0 settings-sandbox.data.microsoft.com
0.0.0.0 watson.live.com
0.0.0.0 statsfe2.ws.microsoft.com
0.0.0.0 corpext.msitadfs.glbdns2.microsoft.com
0.0.0.0 compatexchange.cloudapp.net
0.0.0.0 a-0001.a-msedge.net
0.0.0.0 sls.update.microsoft.com.akadns.net
0.0.0.0 diagnostics.support.microsoft.com
0.0.0.0 corp.sts.microsoft.com
0.0.0.0 statsfe1.ws.microsoft.com
0.0.0.0 feedback.windows.com
0.0.0.0 feedback.microsoft-hohm.com
0.0.0.0 feedback.search.microsoft.com
0.0.0.0 preview.msn.com
0.0.0.0 az361816.vo.msecnd.net
0.0.0.0 az512334.vo.msecnd.net
0.0.0.0 ssw.live.com
0.0.0.0 ca.telemetry.microsoft.com
0.0.0.0 i1.services.social.microsoft.com
0.0.0.0 df.telemetry.microsoft.com
0.0.0.0 reports.wes.df.telemetry.microsoft.com
0.0.0.0 cs1.wpc.v0cdn.net
0.0.0.0 vortex-sandbox.data.microsoft.com
0.0.0.0 oca.telemetry.microsoft.com.nsatc.net
0.0.0.0 pre.footprintpredict.com
0.0.0.0 spynet2.microsoft.com
0.0.0.0 spynetalt.microsoft.com
0.0.0.0 fe3.delivery.dsp.mp.microsoft.com.nsatc.net
0.0.0.0 cache.datamart.windows.com
0.0.0.0 db3wns2011111.wns.windows.com
0.0.0.0 settings-win.data.microsoft.com
0.0.0.0 v10.vortex-win.data.microsoft.com
0.0.0.0 win10.ipv6.microsoft.com
0.0.0.0 ca.telemetry.microsoft.com
0.0.0.0 i1.services.social.microsoft.com.nsatc.net
0.0.0.0 msnbot-207-46-194-33.search.msn.com
0.0.0.0 settings.data.microsof.com
0.0.0.0 telecommand.telemetry.microsoft.com.nsat-c.net