Thinking about the Italian city-states. Venice has a nice position on the sea, with the bays and islands. Genoa also has great sea access. Same with Naples. Pisa is fairly close to the sea.
Florence and Milan don't seem to have sea access. I've read that Florence leveraged it's wool production to become important, and after it was important enough from that industry it was able to move over to banking. (Paint me slightly skeptical, seems that sheep could have been raised in pretty much all of Italy. My family raised sheep for a time so I do have a little bit of knowledge here. Even if Florence had an excellent landrace of sheep, they could have been bought and hauled elsewhere)
So let's say I DO buy that the sheep around Florence combined with the land around Florence was so good that for some reason no one else could really compete in the wool game. That still leaves Milan. What did they leverage to become an economic powerhouse?
(calling them city-states isn't 100% precise, but gets the idea across)
There are multiple reasons which led to Milan becoming a powerful political and economic entity throughout the early modern period.
Like many other cities in the Kingdom of Italy, between the XI and XII century AD Milan underwent a process of political emancipation, as imperial authority had gradually weakened over time. Power shifted (very slowly) from the city bishop to local noble families. By the early XII century, power was mainly in the hands of Consuls (the first "official" consular verdict dates back to 1138, so it is safe to assume that this new institution consolidated in the first decades of the century). Milan thus became what would later be known as a comune, a city ruled by local notable families, de facto independent. This newly-found independence allowed the city to consolidate its power in the region. By mid-century, Milan was one of the most prominent cities in the anti-imperial league formed to oppose emperor Frederick I. The war against the empire ended with the peace of Constance (1183), where the emperor officially recognized the newly-found autonomy of the many cities of the league. Under the rule of the Visconti and Sforza families, Milan remained one of the most important cities in northern Italy throughout the middle-ages. By 1494, after a long conflict with Venice, the city had managed to secure hegemony over a large area in the north-west of Italy.
After the Italian Wars Milan passed under Spanish rule (and there it would remain until the beginning of the XVIII century). The city had immense strategic and logistical value for Spain, since it served as a military staging ground for the numerous wars the crown waged in northern Europe (such as the 30 Years War, or the Dutch War of Independence). As Spanish general Don Carlos Coloma noted in 1626, Milan was indeed "the heart of the [Spanish] monarchy".
In your question, you rightly stated that Milan had no sea access. However, the city was (and has been until fairly recent times) a very important fluvial port. A series of large canals, called *navigli (*some of which are still there today), connected the city to the neighboring large rivers, the Adda (east of Milan) and the Ticino (west of Milan). Both flow into the Po river, which in turn flows into the Adriatic sea. This made Milan a trading hub of great importance.
There is much more to say on the subject, but I hope this was helpful.
Sources:
Sleepwalking into a New World: The Emergence Italian City Communes in the Twelfth Century , by Chris Wickam.
L'Italia e i suoi stati nell'età moderna [Italy and its states in the modern age], by Emanuele Pagano.
Don Carlos Coloma's report to Philip IV (1626)