Tenacious_D: Same problem here (also with Duke Nukem 3d)
I tried re-downloading/enabling compatibility mode/ run a admin but that wouldn't wok either, incidentally I tried it on a different computer (Netbook Win7 Version?) and while I couldn't get into the game I was able to run setup.exe.
Gonna try it on a different/older PC over the weekend.
EDIT:
You can access the setup via the Start menu button and go to the folder named 'GOG.com'. There, in the game's folder you'll find a working setup.exe
Sloopydrew: News to me. I can't get a working version, no matter where or how I access it. It just keeps giving me the "file not compatible" error -- as an admin, in different compatibility modes, etc. etc. etc.
I would recommend doing a clean (re)instal of Blood without the compatability tweaks.
Then go to START->Gog.com->One Unit whole of Blood->Setup
Try out if it works. If it does you should see a DOSBOX prompt that takes you to the Setup.
If it doesn't:
Rightclick Setup->Properties and check the path, it should somewhat look like this (I think)
"D:\One Unit Whole Blood\DOSBOX\dosbox.exe" -conf dosboxBlood_setup.conf -noconsole
Copypaste the -conf blahblahblah part if necessary.
I hope this helps.