Which was the federations greatest enemy?

Borg then dominion

 

I would have to think Klingons. They had a decades-long cold war and at least 3 wars.

 

I would assert that the Federation was the Federations greatest enemy, particularly the view of themselves in respect to the universe. Starfleet was a concentration of that.

 

I second this. They had the Federation and the Klingons break their peace treaty and at each others throats, and reeked enough havoc internally with just four Founders that the Federation imposed martial law onto themselves.

Plus the Founders were practically worshiped by the Dominion and were the only ones who could really bring an end the Dominion war.