Problem 1:
When attempting to run an application that uses certain Telerik controls, you may run into the error below:

System.InvalidOperationException:
‘~/Telerik.Web.UI.WebResource.axd’ is missing in web.config.
RadStyleSheetManager requires a HttpHandler registration in web.config. Please,
use the control Smart Tag to add the handler automatically, or see the help for
more information: Controls > RadStyleSheetManager at
Telerik.Web.UI.RadStyleSheetManager.OnPreRender(EventArgs e) at
System.Web.UI.Control.PreRenderRecursiveInternal() at
System.Web.UI.Control.PreRenderRecursiveInternal() at
System.Web.UI.Control.PreRenderRecursiveInternal() at
System.Web.UI.Page.ProcessRequestMain(Boolean includeStagesBeforeAsyncPoint,
Boolean includeStagesAfterAsyncPoint)


Solution:
I’ve seen that error on new DotNetNuke installations but it certainly isn’t specific to DNN, nor is it a problem with the Telerik controls. The issue is that the Integrated Pipeline Mode and Classic Modes handle the registration slightly differently within the web.config file.
To resolve this error you can make changes to your web.config file, or, a perhaps faster and easier solution, is to change your site’s ASP.NET version to Classic Mode – both seem to work equally well.

Problem 2:
When you place RadScriptManager on aspx page and compile it gives error like, 

" '~/Telerik.Web.UI.WebResource.axd' is missing in web.config. RadScriptManager requires a HttpHandler registration in web.config. 
Please, use the control Smart Tag to add the handler automatically, or see the help for more information: Controls > RadScriptManager "


Solution:
Its Simple And fast you Just Have to register The radScriptmanager and it will modify the web config file automatically.

  • Click RadScriptManager Menu Cursor .It Will Display RadScript Manager Tasks click on Regiter Telerik.Web>UI.WebResource.axd
Telerik.Web.UI.WebResource.axd
  • Telerik.WebUI.WebResources.axd Is Now Succeessfully Register in Web Config.

    Telerik.Web.UI.WebResource.axd