If I were to install and run Debian Linux from an SD card or microSD card, would this be less reliable than running from a regular HDD (e.g. a 2.5" Western Digital Blue)? The system and home folders would all be placed on the SD card.
It will only be limited by the quality of the SD card and slot. The SD card should at least have a much lower latency than your rotating hard drive.
This is an approved Debian installation method, as shown here: