Yes.. but you'll need to run them using .Net 2.0 App pool, which doesn't provide the same safety considerations as 4.0.

With 2.0, all web apps run in the same pool, so if one crashes, it can bring down all the other web apps. Under 4.0 app pool, each app can run in its own app pool.

>Do you know if it is possible to run two application in the same site where the application that runs in main/parent folder is compiled in .NET 2.0 or in sub-folder in .NET 4.0?
>
>For example:
>MainSiteName - ASP.NET 2.0
>MainSiteName\SubApp - ASP.NET 4.0
>
>So the user can start the 2.0 application as MainSite\Main20Page.aspx and can start 2.0 application as MainSite\SubApp\Main40Page.aspx?