I finally encountered this issue myself on a machine and after a lot of investigation I finally found the cause and solution.
The solution is you must install ASP.NET 2.0 AJAX 1.0 in the GAC (Global Assembly Cache), by using the msi installer for MS AJAX 1.0.
mojoPortal includes the System.Web.Extensions.dll file in the bin folder but in Medium Trust it can't run from the bin folder it has to be in the GAC on the server. If it is installed in the GAC it will ignore the one in the /bin folder so it doesn't hurt for it to be there but you can safely delete it.
So the reason I could not produce this problem on my machine in medium trust is because I already had this installed. When I encountered this on a different machine I finally was able to pin down the problem.
Hope it helps,
Joe