Often Platinum will stop responding when I try to save larger projects, causing all work to be lost and forcing me to kill the SONARPLT.exe process.  After this happens, an instance of a TMP file is left behind in the project folder (e.g. MFC14DC.tmp).
 
Win7 64, happens across multiple interfaces.  Version 21.00.01 BUILD 254 (x64).  Anyone else experience this or have any possible workarounds?

Never had this issue myself. Try turning on auto versioning in preferences. I rarely need to go back to an old version but nice to have the option. This would serve as some protection of your mixing progress while you work out why you are getting freezes.

How full or old is your hard drive?

What is the size of your project file?

It's so hard to know what to recommend when no one else has reported a similar problem, because that implies a system- or project-specific issue, and there's virtually no information about the system. For example maybe you have your operating system, SONAR, and all your projects on a C: drive that's close to full. It's always good practice to have a separate data drive.
 
Try "Save As" to a USB stick of sufficient capacity, and see what happens. 
 
Also, "SONAR never forgets." A project size will balloon as you do more operations and SONAR saves more files so you can undo. If you "Save As" to a new folder and save all audio, then you can delete the older (and much larger) project. For example, I'll often have a project grow to 3-4 GB just prior to mixing. After saving as, it will be more like 200-300 MB. Of course if the hard drive is close to full, a Save As may push the drive over the edge because the two projects will co-exist until you delete the older one.
 
It could also be a hard drive getting close to failing.
 
If it's not related to your hardware, a plethora of weird problems can crop up due to driver conflicts and such. Make sure all your drivers, including your graphics card drivers, are up to date. Then, check how many audio drivers are listed in Device Manager under "Sound, Video, and Game controllers." Disable all but the one you're using for your ASIO interface.
 
Finally, as a diagnostic next time this happens, walk away from the computer and come back 15-20 minutes later. What state is SONAR in when you return?

I'm beginning to suspect particular plugins, though I haven't narrowed it down to which ones yet.  Hard to say if the upgrade was even the root cause anymore - thanks for the suggestions, I'll report back if I figure anything else out.

Well I reported a similar issue where Plt would just crash to the desktop upon saving on a number of occasions...and also stopped responding as well forcing me to kill it - felt like doing that as well!
 
Turns out that Kontact and in particular 'Alicia's Keys' and 'Session Horns' modules were causing the grief and apart from a Melodyne crash, it's been pretty stable since I've stopped using them.

I had the same problem with NI plugs being the culprit....not all of them mind you, just one Session Strings Pro....it played and recorded fine, but always crashed Sonar if I tried to save, freeze, or bounce. Tried for years to fix this....NI totally unhelpful.....no answers in forums, although I have run across a few users with the same issue.....so $299 wasted....I gave up the headache long ago

Yup not only update drivers (esp your audio interface) but your firmware.
Also run windows update.
Then take a look at your plugins...
 
Full system specs please.
 
Thanks...

Had the same problem. Lost 2 projects after Platinum down load.