ClickOnce is currently a very undersupported technology in my opinion. Currently only Internet Explorer can natively execute it, and FireFox if you use the FFClickOnce add-on.
My questions are multiple (after an edit):
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Does anybody know of supported methods to open ClickOnce applications from Opera/Safari/Chrome?
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If not, where would one begin in creating a usable, robust plug-in to achieve this functionality.
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Where would one start in making FireFox, Safari and Opera extensions?
I guess this boils down to explaining how a ClickOnce application is in fact launched, as well as if the browser frameworks can support it.
Also, with Chrome, I understand there is no add-on infrastructure, so if no answers exist for it, I fully understand.
This used to be the case but isn’t anymore: .NET Framework 3.5 SP1 does install its own add-on for this purpose (see .NET Framework Assistant for Firefox). Whether you consider this to be ‘native’ support or not is up to you, but of course it’s still a regular add-on, though being officially released and supported by Microsoft helps a lot to improve Firefox user experience in regard to ClickOnce applications.
Obviously, in order to facilitate this new official Firefox add-on, the .NET Framework 3.5 SP1 must be bootstrapped by itself in case users don’t happen to have it already, but this is another topic and doesn’t differ much from installing any other baseline technology. It’s worth nothing though that there has been improvements in this area too: By means of the .NET Framework Client Profile (see related FAQ too) many applications can reduce deployment size significantly (apparently ~28 MB instead of ~230 MB for the full framework).
Other then some questionable workarounds I’m not aware of any robust solutions.
Your first stop regarding ClickOnce development (available for .NET 2.0 and higher) should be ClickOnce Deployment for Windows Forms Applications (the name is misleading, ClickOnce is not limited to Windows Forms). You’ll find a wealth of information there on how to use the ClickOnce API, both implicitly via the build in deployment tools and especially programmatically from your own applications. The latter seems to be rarely used so far, unfortunately, though it is actually quite powerful. Consequently you should be able to include this functionality in almost any kind of 3rd party application, including browsers of course, as long as those do provide any kind of plug-in architecture.
I understand (and applaud) your approaching this issue from the single angle of end user ClickOnce experience, still I think given the broad scope of the topic it should best be asked in a separate question, if not in a separate question per browser even. That said, there are quite some related questions to be found on Stack Overflow already, see e.g. for Firefox (most obvious 😉 questions/tagged/firefox+add-on and questions/tagged/firefox+extension.