Even the latest DNN reference is system.web.extensions.dll version 1.0.61025.0 which is the previous version of aspajax. in Framework 3.5 it has been migrated.

and in the previous version, many 3.5 controls're had no idea to use such as ListView.

It is possible, if I understand you correctly.

Check my blog post : http://it.tmod.pl/Blog/EntryId/135/DotNetNuke-in-Medium-Trust-environment.aspx .

It's about running DNN in medium trust environment, but the key of it is to change System.Web.Extension.dll to version 3.5.

Unfortunately LinqPrep will only upgrade the Linq references. For the System Web extensions you will need to make the following changes AFTER running LinqPrep :

• Remove the System.Web.Extensions.dll file from the bin directory in your DotNetNuke website.
• Modify the web.config of your DotNetNuke site:

ADD to <configSections>:

<sectionGroup name="system.web.extensions" type="System.Web.Configuration.SystemWebExtensionsSectionGroup, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35">
<sectionGroup name="scripting" type="System.Web.Configuration.ScriptingSectionGroup, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35">
<section name="scriptResourceHandler" type="System.Web.Configuration.ScriptingScriptResourceHandlerSection, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" requirePermission="false" allowDefinition="MachineToApplication"/>
<sectionGroup name="webServices" type="System.Web.Configuration.ScriptingWebServicesSectionGroup, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35">
<section name="jsonSerialization" type="System.Web.Configuration.ScriptingJsonSerializationSection, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" requirePermission="false" allowDefinition="Everywhere"/>
<section name="profileService" type="System.Web.Configuration.ScriptingProfileServiceSection, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" requirePermission="false" allowDefinition="MachineToApplication"/>
<section name="authenticationService" type="System.Web.Configuration.ScriptingAuthenticationServiceSection, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" requirePermission="false" allowDefinition="MachineToApplication"/>
<section name="roleService" type="System.Web.Configuration.ScriptingRoleServiceSection, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" requirePermission="false" allowDefinition="MachineToApplication"/>
</sectionGroup>
</sectionGroup>
</sectionGroup>

Change: the <system.codedom> section to:
<system.codedom>
<compilers>
<compiler language="vb;vbs;visualbasic;vbscript" type="Microsoft.VisualBasic.VBCodeProvider, System, Version=2.0.0.0, Culture=neutral, PublicKeyToken=b77a5c561934e089" extension=".vb" warningLevel="4">
<providerOption name="CompilerVersion" value="v3.5"/>
<providerOption name="OptionInfer" value="true"/>
<providerOption name="WarnAsError" value="false"/>
</compiler>
<compiler language="c#;cs;csharp" extension=".cs" type="Microsoft.CSharp.CSharpCodeProvider,System, Version=2.0.0.0, Culture=neutral, PublicKeyToken=b77a5c561934e089" warningLevel="4">
<providerOption name="CompilerVersion" value="v3.5"/>
<providerOption name="WarnAsError" value="false"/>
</compiler>
</compilers>
</system.codedom>