mojoPortal requires at minimum .NET 3.5 sp1 though that is really just 2.0 with some additional things.
If you are not using .NET 4 then you need to use one of the Web.config files for 3.5 ie Web.net35.config or Web.net35.mediumtrust.config
See also The .NET 4 Transition Plan and the 9th and 10th items in our FAQ.
My advice to anyone is to use .NET 4, it has been out for a long time and has many benefits over 3.5 and eventually we will drop support for .NET 3.5, so I would advise using .NET 4 especially for any new sites. For example if you use .NET 3.5 under medium trust you will not be able to use more than one skin because VirtualPathProvider don't work under .NET 3.5 medium trust and it means that all skins will use the theme.skin file from /App_Themes/default instead of the one in the skin folder, and therefore all skins will have the same settings and that causes problems where skins may not render correctly.
Hope that helps,
Joe