I'm editing the original post because I've figured a few things out, so my question can be more specific.
I'm working with the AjaxControlToolkit and Visual Studio 2015 Community edition. I used NuGet to install the toolkit and the Html Sanitizer they suggested.
Now, I set up a web forms ASP.NET page containing the HtmlEditorExtender control, and it works fine except for the embedded AjaxFileUpload control.
The upload is failing, and I included the console output below to show what I get.
It appears that the error comes because the app can't find the AjaxFileUploadHandler.axd file (that's what the more descriptive version of the console message is). I tried all of the suggestions I could find about modifying the web.config file (here are the relevant sections):
<system.webServer>
<validation validateIntegratedModeConfiguration="false" />
<handlers>
<add name="AjaxFileUploadHandler" verb="*" path="AjaxFileUploadHandler.axd" type="AjaxControlToolkit.AjaxFileUploadHandler, AjaxControlToolkit" />
</handlers>
<security>
<requestFiltering>
<requestLimits maxAllowedContentLength="4294967295" />
</requestFiltering>
</security>
and...
<system.web>
<trust level="Full" />
<httpHandlers>
<add verb="*" path="AjaxFileUploadHandler.axd" type="AjaxControlToolkit.AjaxFileUploadHandler, AjaxControlToolkit" />
</httpHandlers>
I've uninstalled the toolkit, rebooted the server, tried everything I could find on it, and yet still no joy. I'm out of ideas here. Any help from anyone, please?

If you host your application no at the root of a web site, you need to specify a path to the
AjaxFileUploadHandler.axdthat includes all path parts after the site root.For example, if you host a site at
http://mysite/myapp/mypage.aspxyou need to define it like that:You can also see this issue for more details: https://github.com/DevExpress/AjaxControlToolkit/issues/43#issuecomment-203889967