Broadly, handbrake supports far less customization, accepting fewer source formats, and outputting fewer destination formats than FFmpeg does. This specificity allows Handbrake to do more work to understand input videos at a deeper level than FFmpeg defaults to. For instance, FFmpeg includes options to concatenate, slice, superimpose, or filter multiple videos while Handbrake only slices the input. Similarly, Handbrake includes options to select or burn-in certain language subtitles tailored to the needs of TV show or anime watchers; FFmpeg defaults to copying only the first stream unless told otherwise.
As a second example, Handbrake only supports h264, h265, AV1, and a couple MPEG codecs. This means Handbrake can convert HDR video; it extracts that data and supplies it to the output encoder automatically, while FFmpeg doesn't do that for you.
