I have resolved the issue, atleast for my sites, by recompiling the DotNetNuke.HttpModules.dll. Under UrlRewriteModule.vb I changed the following line:

If New PortalController().GetPortals().Count = 1 Then

to:

If New PortalController().GetPortals().Count >= 1 Then

The error occurs because the sub does not know the portal ID, the portalID is set to the host portalID via:
        'the domain name was not found so try using the host portal's first alias
        PortalId = Host.HostPortalID

If the portalID is not null then a PortalController returns the number of portals and only if there is 1 portal is the PortalAliasInfo object created and assigned to "objPortalAliasInfo". However my site has more portals so the PortalAliasInfo is never assigned.

So we leave this section of the sub and continue to an if statement block thats asks if the portalID is known (not -1). The portalID is now known because it was set above, however the PortalAliasInfo isn't known. A New PortalSettings object is created using the PortalAliasInfo that is not assigned which causes the exception.

I did run into an issue that was not existant on my 05.05.01 installation after resolving this issue. I run a web application using iframes through DNN and some of the pages are named similarly to my Friendly URL pages (home.aspx for example). If they have the same name the IFrame will now display the DNN page rather than my application's page. I worked around this by simply adding an underscore to my application's page's names.

'objPortalAliasController.AddPortalAlias(objPortalAliasInfo)
'If app.Request.Url.AbsoluteUri.StartsWith("https://", StringComparison.InvariantCultureIgnoreCase) Then
    'strURL = "https://" & objPortalAliasInfo.HTTPAlias.Replace("*.", "")
'Else
    'strURL = "http://" & objPortalAliasInfo.HTTPAlias.Replace("*.", "")
'End If
'Response.Redirect(app.Request.Url.ToString(), True)