You mentioned registry, so I'm going to go back through the steps you should go through.
You've already downloaded TTD (Assumedly the windows version), and you've downloaded the patch, but I'm guessing you've downloaded the old stable version of the patch. With the old patch, the game requires registry information created during the CD's installation process, since you downloaded TTD, it probably didn't have the installer. Newer versions of TTDPatch allow running the game without having any registry information stored on the computer, it uses some voodoo magic and reads its registry information from a file called registry.ini (Which new versions of TTDPatch create automaticly)
What you need to do is download the most recent beta version from http://www.ttdpatch.net/src/
. Don't let 'Development Version' discourage you, the betas are pretty damn solid.
While you're are it, to properly enjoy a lot of the new features added to the recent ttdpatch versions, you will need the base graphics file. Download that from here: http://www.ttdpatch.net/newgrf.html#25
Make sure that you have also disabled the Win95 compatibility mode on the program's properties, you do-not need it. TTDPatch includes support for newer versions of Windows by default.
Now, assuming those instructions have been followed (I won't treat you like an idiot by explaining how to install ttdpatch, you've already done it once and gotten far enough for the game to complain about registry, which generally only TTDPatch will do. If you're not running ttdpatchw.exe and you get errors, it will be errors about not finding the CD), the game should run properly by just double clicking ttdpatchw.exe. If you are still getting the registry issue, try deleting 'registry.ini' and running ttdpatchw.exe again. That also counts if you were already running the 2.5 betas when your registry issue came up.