But the Genoese did capitulate various times in their history: Genoa first submitted to the voracious Visconti of Milan in the 14th century, and also suffered bouts of occupation from the Spanish and French in the 16th century.

The Genoese, like many other Italian polities, were able to preserve institutional continuity through foreign occupations. What this meant was that the political and administrative organization of the Genoese state remained intact even if the Republic's leadership became dependent on (or subject to) an outside occupying power. But even while nominally independent, the Genoese proved themselves more than willing to defer to political reality and expediency in order to preserve the Republic's social-political system, best exemplified in the 16th century when the Geonese ruling class strongly integrated itself with the Spanish Empire's system of colonial domination both in and out of Europe. What the Genoese did was explicitly sacrifice the political autonomy of the state in order to link themselves to an economically advantageous system and guarantee prosperity. So in the 16th century, Genoese trading houses establish themselves in Seville, Valencia, and Madrid, where in addition to ordinary commerce they would also participate in backing expeditions to the New World, all the while forgoing any sort of political, territorial, or even institutional changes to the Genoese state itself.

So in the grand designs of 16th and 17th century Great Powers of Europe, the Republic of Genoa was effectively an appendage of the Spanish Empire. And this manifested itself in more ways than one: not only were Genoese merchants and bankers well-integrated in the Spanish empire's economy (and Genoese aristocrats in the Empire's officer corps, especially the Navy) the harbor of Genoa itself was a major component of the Northern Italian node through which Spanish power was projected into Italy and Central Europe. Indeed, just to the north of Genoa was the city of Milan, a direct Spanish possession which housed one of the Empire's largest fortresses. Garrisons in Milan, be they stationed long-term in Lombardy or mustering to march into Central Europe, were necessarily supplied from Spain out of the Genoese harbor. And supply lines to and from Genoa would remain important as Spanish armies set out from the fortress of Milan, to march over the Telline Valleys into anywhere in Central Europe (a major route through the Eighty Years War and the Thirty Years War). The Genoese were in no way averse to the arrangement, and if they had somehow been uncomfortable or unhappy with their role in the imperial system what could they even have done? What would this achieve beyond the death or exile of the city's most important political leaders, exclusion from the Empire's mercantile affairs, and an inevitably violent and highly disruptive forced subjugation by force of arms? In other words, to which end or benefit would they disrupt their role in the Spanish Empire's system of power projection?

We can, if we'd like, pick the War of Spanish succession as a key inflection point in Genoa's autonomy. The empire's heyday was long gone, and the conflict demonstrated the definitive end of the Spanish crown's ability to project power. Why didn't anyone gobble up Genoa in Spain's moment of greatest weakness? The answer, as unsatisfying as it might be (we are dealing, of course, with a counterfactual which will always be somewhat unsatisfying as these answers are almost always permutations of, "Because it didn't") I propose the crux of the same question I asked of possible Genoese resistance against the Spanish Empire in the first place: What would be gained?

The city was indeed subject to both French and Austrian sieges, bombardments, and occupations over the course of the first half of the 18th century. But how many resources would it take to fully occupy, annex, and integrate the Republic? At war's end, who would want to sit at a negotiating table and find the political will to argue that they'd like to be granted the Republic of Genoa? Would the seizure be worth whatever concessions the other side demanded?

The answer is "Probably Not" (or, because we know that no one did so, "Absolutely not.") The extractive policies of the Spanish Empire had run their course for Genoese investors, while the Mediterranean trade routes the Genoese floridly participated in had been eclipsed in value by in the North Atlantic. The powers of the European Continent (Austria and France) did not need Genoa's harbor to project power. Genoa was not even a "dynastic jewel" which could augment a ruling dynasty's prestige or perception.

So fundamentally, Genoa was left alone much like the rest of Italy was (indeed we could ask your same questions of Tuscany, the Savoyard State, and a manner of other places in Italy). It is only after the Napoleonic wars that the Savoyard Kings of Sardinia venture a claim to absorb the Republic, and the great powers of Europe are happy to grant it: in spite of their future fame as unifiers of Italy, the restoration-era House of Savoy was highly conservative and well-aligned in political interests with the Austrian Empire. The great powers of the Congress of Vienna, who had no use for Genoa as we have established, were happy to grant the Republic to the Savoyards.