First, due to privacy/security concerns,I simply do not use the cloud. Nothing online is safe nowadays, so I prefer having direct control over my devices, content, and availability. Additionally, it is quite common for people to think that icloud is a true backup solution - it sounds like it would be, but it is simply a way Apple has provided to allow access to your files across other devices. I was introduced to it when I set up a new Mac and purposely skipped over the icoud setup. What I did not know is that it automatically took all of my contacts and parked them in cloud. I found that by trying to find a contact and they had all disappeared from my Mac. When I checked icloud, they were there. It took a while to get them back to my Mac.
So, yes, if you have a clone - and, as long as you do not update that after you deleted things from your drive - it is fine to delete whatever files you want. Just be aware, if you "prune" your internal, the next clone will reflect that content - unless SD has the capability to retain older files (CarbonCopyCloner does provide that option). I use CCC, so I am not sure of SD.
As for assuming it is safe to upgrade, everyone's machine and content are different, so someone may experience a glitch just because there is some software that is incompatible or instance. Generally, yes, it is safe as long as you realize that none of your 32 bit apps will work. As for MS products, I can't help since I've never used any. And no, other than checking with developers on any updates, there isn't an easier way. You can use the www.roaringapps.com website as well, they maintain lists of what is compatible with what.
And, an additional thought on upgrading: I would use an external hard drive to clone my current system to and then update the internal to Catalina, which is essentially what you are doing. So, upgrade, and test drive it. Be aware that Catalina changes the file system to AFPS with two volumes: mac HD (visible, but read only, contains the OS and system) and Mac HD - Data (read/write, contains apps, your user folder, etc). If you ever want to revert or reinstall, you will need to wipe the entire thing or you will wind up with one or more extra duplicate Data volumes. That new filing system is, at best, utterly confusing. So, I'd get myself another external hard drive for backups so you keep your previous backups and the new AFPS backups separate.
Lastly, I do not use Time Machine, but I believe that any external disk for it must be Mac OS Extended (Journaled), not AFPS l- best if you check on that here or with Apple support.