We stayed for a week in an AirBnb in Harlem on West 122nd St. We used the A train from 125th St quite a lot and also used a couple of buses.
We walked down Fred Douglass Boulevard and shopped at the Lidl down there, as well as at local delis. We ate and drank in the evening at a couple of the restaurants there around 116th St.
On the Sunday we walked down to Redeemer East Harlem on East 116th St and were welcomed warmly, followed by a lunch at a great Senegalese restaurant not too far from there.
Although there were a slightly higher number of obviously homeless persons on the street, we felt perfectly safe, never threatened.
Like any big city, just keep a good amount of situation awareness.
This was our first visit but I am sure it won't be the last.