CarbonCopyClone/SuperDuper clones are critical to being able to rebuilld your OS in case of disaster.
Smaller "boot partition" that is not loaded with application data does backup/restore more quickly than larger data volumes.
Also you should keep 10%-15% of your system partition free for OSX to have "playroom" ... another argument for not storing files that eat up many 10s or 100s of MB at a gulp like photos.
So ... my humble opinion ...
If you *can* have multiple disks and store data separate from boot-disk, I would try it for a while at least until "inconvenince" proves another strategy is needed.
FWIW, I use a relatively small (120GB) SSD for my boot drive containing only my "key" apps but my home dir and any other third party apps are kept on one of my internal 2TB Western Digital blacks. I use Carbon Copy Cloner for daily backups of both drives to a third internal 2TB (and less frequently to an external 2TB).
For the boot drive always assume you need about 20GB to 25GB of space (I don't use minimum capacity percentages given the capacity of drives has risen over the years). Obviously 120GB for my boot drive is way overkill unless I have a lot of "key" apps I want to stick on there (and I don't).