Okay cool. After updating to .net 4.5, you went back to the mining console and tried hitting Register Mining Module, then click refresh a few times right? If not go and try that. If you already did, then with Gridcoin open, try this:
Open an administrator prompt and enter the following.
regasm boinc.dll
regtlibv12 boinc.tlb
They should both return successful. Then go to the Mining Console and hit refresh a few times. You should see the Registered Mining Module Version go up, as well as the Threads and Processing Power.
If that doesn't work, then delete the folder you extracted the .zip to, and install the .msi, as it does the registering automatically.
Yeah one point Id like to make, when you install from the zip and do the manual registration of the files, if your mining console Registered Version is "0", the client is NOT going to work. You have to get that number above zero. When you click "Register" from the client, it will technically do the commands Aysyr listed but that only works if you are running the program as admin and you have Unblocked the downloaded files (to mark them as safe). Next, if you do the manual registration from the command prompt you have to run these commands from the gridcoin-qt.exe's location (ie CD to the gridcoin folder first). If all this fails install the program using the MSI as Aysyr pointed out and it will auto-register.
Good luck.