Valid C of O necessary?

The most important one is that if the house was used as an SRO (single room occupancy) any of the people that stayed there (paying) for more than 3 months in the past can demand you give them back a room, or ask for money, particularly in the case that any of the previous owners harassed them to leave. That´s why the owners usually produce a certificate of non harassment, even if they never had used it as an SRO.

mimi - wow. the things you learn on SE...

What if a house is Zoned for S2(2 family plus commercial/small office) and you rent it out accordingly but it does not have a valid C of O on file at the DOB. Can the DOB fine you for not having a valid C 0f O and force you to get one?

No, that's very common and totally legal. What the agent told you was true. You should find this to be a non-issue.