Quick answer:
C:\Program Files\WSPBuilder\WSPBuilder.exe.config
(or where ever you've installed it)
add key="BuildSafeControls" value=""
Long answer:
WSPBuilder is great for when you want to do a quick deployment via Visual Studio to your SharePoint installation. I have found that that it gets harder to configure when you need to deploy CAS policies but I'm sure they will do work in this area for future versions.
WSPBuilder in your scenario can automatically build and deploy the safecontrol entries that need to go into your site. Good thing about WSP's are that once you retract a solution, it will also go back and remove the safecontrol entries so you don't need a tidy up job.
Regarding different projects, if you need to install third party wsps, then WSPBuilder hasn't been designed for that purpose, I suggest a simple batch file with some stsadm commands. If some of these solutions are your own code, you should divide each into a different VS project and build their WSP's seperately. You may even need to divide them into different .sln (solution files) but I've not tried this way myself so couldn't say for sure.
Personally, I would only use use WspBuilder to build deployment packages that need to be deployed to live environments if I can be sure its not adding extra bits that may become a problem. Therefore you'll need to think about WSPBuilder wsp's are good enough for you.
Recently I came accross an issue with CAS policies and decided to make my WSP's manually. Under the hood, WSP files are CAB files, you can just create a CAB file and rename its extention to .WSP. I would advise, creating a WSP, rename it to mysolution.cab. Open it and up and extract the files, and have a look to see whether its doing what you want. Key file to look at: manifest.xml.