Malta sends boats out from four harbours on the main island plus two on Gozo, and they are not interchangeable. The distance from your quay to Comino is the single biggest variable in a Maltese boat day.
Sliema Ferries is the busy one. The boats load from the promenade on The Strand, between the Fortina and the Marsamxett ferry terminus, and this is where the big shared cruisers sail from — the seven-hour Comino and Gozo day, the Gozo coastal loop, both round-Malta cruises. It is walkable from most of Sliema and St Julian's and it is the easiest pier to reach in Malta. The price of that convenience is distance: Sliema sits on the eastern side of the island, so the boat needs roughly ninety minutes each way to reach Comino. Three of your seven hours are transit.
Bugibba Jetty, in St Paul's Bay, is the north-coast alternative and a scheduled second pickup on several Sliema sailings. The catamaran and the top-rated coastline cruise both start here. From Bugibba the crossing is 45 minutes to an hour, so the same lagoon costs you an hour and a half less of sitting still.
Ċirkewwa Ferry Terminal, at the northern tip of the Marfa Ridge, is where the public boats live: Gozo Channel's car-and-passenger ferry to Mġarr, and the Comino Ferries and Ebsons boats to the Blue Lagoon. Marfa, the small landing a few minutes down the same road, runs the same Comino service. Neither is a tour — they drop you and leave. From here Comino is twenty minutes away, which is why the small-group tours that start in Mellieħa and Marfa can deliver a whole trip in three or four hours. Bus routes 41, 42, 101, 221, 222 and X1 all terminate at Ċirkewwa; Malta Public Transport's single fare is €2.00 in winter and €2.50 from mid-June to mid-October, valid two hours with a free transfer.
The Grand Harbour at Valletta sends out no Comino day boat at all, and that surprises people who booked a hotel in Valletta. What it does have is Lascaris Wharf, below the Upper Barrakka lift, where Gozo Highspeed's passenger catamaran runs to Mġarr on Gozo in about 45 minutes, and where the Three Cities ferry crosses to Cospicua. The Sliema ferry uses the Marsamxett side of the peninsula instead — a different waterfront, a five-minute walk apart at the top, twenty minutes apart at sea level. Mġarr Harbour on Gozo is the last piece: the private speedboats, and the half-day cruises for people already staying on Gozo, load there.