Yes. 4.5 replaces 4.0. There may be some subtle differences.

BTW, this looks like a .Net issue, not a VS issue. Do not confuse the two. While VS is tightly bound to .Net, there is nothing that requires you use VS to develop .Net apps. You could write all your code in NotePad and still compile and run it.

>Right now, my framework and my client projects are set to .NET Framework 4.0. Even with that setting, do I really need the .Net 4.5 runtimes?
>
>Here is more information. I set the registry HKEY_LOCAL_MACHINE\SOFTWARE\Microsoft\Fusion EnableLog to 1. This gives me more information:
>
>=== Pre-bind state information ===
>LOG: User = something\something
>LOG: DisplayName = Framework
> (Partial)
>WRN: Partial binding information was supplied for an assembly:
>WRN: Assembly Name: Framework | Domain ID: 2
>WRN: A partial bind occurs when only part of the assembly display name is provided.
>WRN: This might result in the binder loading an incorrect assembly.
>WRN: It is recommended to provide a fully specified textual identity for the assembly,
>WRN: that consists of the simple name, version, culture, and public key token.
>WRN: See whitepaper http://go.microsoft.com/fwlink/?LinkId=109270 for more information and common solutions to this issue.
>LOG: Appbase = file:///D:/iis/Universal Thread/
>LOG: Initial PrivatePath = D:\iis\Universal Thread\bin
>Calling assembly : (Unknown).
>===
>LOG: This bind starts in default load context.
>LOG: Using application configuration file: D:\iis\Universal Thread\web.config
>LOG: Using host configuration file: C:\Windows\Microsoft.NET\Framework64\v4.0.30319\aspnet.config
>LOG: Using machine configuration file from C:\Windows\Microsoft.NET\Framework64\v4.0.30319\config\machine.config.
>LOG: Policy not being applied to reference at this time (private, custom, partial, or location-based assembly bind).
>LOG: Attempting download of new URL file:///C:/Windows/Microsoft.NET/Framework64/v4.0.30319/Temporary ASP.NET Files/universalthread/c9af4643/2449e21f/Framework.DLL.
>LOG: Attempting download of new URL file:///C:/Windows/Microsoft.NET/Framework64/v4.0.30319/Temporary ASP.NET Files/universalthread/c9af4643/2449e21f/Framework/Framework.DLL.
>LOG: Attempting download of new URL file:///D:/iis/Universal Thread/bin/Framework.DLL.
>ERR: Failed to complete setup of assembly (hr = 0x8007000b). Probing terminated.
>
>And, then, the StackTrace as before:
>
>[BadImageFormatException: Could not load file or assembly 'Framework' or one of its dependencies. An attempt was made to load a program with an incorrect format.]
> System.Reflection.RuntimeAssembly._nLoad(AssemblyName fileName, String codeBase, Evidence assemblySecurity, RuntimeAssembly locationHint, StackCrawlMark& stackMark, IntPtr pPrivHostBinder, Boolean throwOnFileNotFound, Boolean forIntrospection, Boolean suppressSecurityChecks) +0
> System.Reflection.RuntimeAssembly.InternalLoadAssemblyName(AssemblyName assemblyRef, Evidence assemblySecurity, RuntimeAssembly reqAssembly, StackCrawlMark& stackMark, IntPtr pPrivHostBinder, Boolean throwOnFileNotFound, Boolean forIntrospection, Boolean suppressSecurityChecks) +210
> System.Reflection.RuntimeAssembly.InternalLoad(String assemblyString, Evidence assemblySecurity, StackCrawlMark& stackMark, IntPtr pPrivHostBinder, Boolean forIntrospection) +242
> System.Reflection.RuntimeAssembly.InternalLoad(String assemblyString, Evidence assemblySecurity, StackCrawlMark& stackMark, Boolean forIntrospection) +17
> System.Reflection.Assembly.Load(String assemblyString) +35
> System.Web.Configuration.CompilationSection.LoadAssemblyHelper(String assemblyName, Boolean starDirective) +122
>
>[ConfigurationErrorsException: Could not load file or assembly 'Framework' or one of its dependencies. An attempt was made to load a program with an incorrect format.]
> System.Web.Configuration.CompilationSection.LoadAssemblyHelper(String assemblyName, Boolean starDirective) +12761078
> System.Web.Configuration.CompilationSection.LoadAllAssembliesFromAppDomainBinDirectory() +503
> System.Web.Configuration.AssemblyInfo.get_AssemblyInternal() +142
> System.Web.Compilation.BuildManager.GetReferencedAssemblies(CompilationSection compConfig) +334
> System.Web.Compilation.BuildManager.CallPreStartInitMethods(String preStartInitListPath) +203
> System.Web.Compilation.BuildManager.ExecutePreAppStart() +152
> System.Web.Hosting.HostingEnvironment.Initialize(ApplicationManager appManager, IApplicationHost appHost, IConfigMapPathFactory configMapPathFactory, HostingEnvironmentParameters hostingParameters, PolicyLevel policyLevel, Exception appDomainCreationException) +1151
>
>[HttpException (0x80004005): Could not load file or assembly 'Framework' or one of its dependencies. An attempt was made to load a program with an incorrect format.]
> System.Web.HttpRuntime.FirstRequestInit(HttpContext context) +12881540
> System.Web.HttpRuntime.EnsureFirstRequestInit(HttpContext context) +159
> System.Web.HttpRuntime.ProcessRequestNotificationPrivate(IIS7WorkerRequest wr, HttpContext context) +12722601