He came running towards me.
He came towards me running.
Do you find both of the sentences natural? Can we use both the sentences interchangeably?
The first is far more natural to my ear.
The second expresses essentially the same meaning, but emphasises his mode of locomotion rather than his destination - it emphasises that he was running, as opposed to, say, skateboarding or cartwheeling. Since running is by far the more obvious verb in such a scenario, it sounds rather odd to emphasise it this way. The only situation I can easily imagine using your second sentence is in poetry or literature.
Note that it is however natural to use a non-locomotion verb in that position, for example "He came towards me shouting". This is because the locomotion verb is implied, "He came [running/walking] towards me [while] shouting".