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Santander acrobatically nodded home with two minutes remaining of a free-wheeling encounter to take the three points after Carlo Ancelotti's side had gamely fought back from two goals down at half-time.
The Paraguayan also opened the scoring with a towering header two minutes before half-time and laid on Blerim Dzemaili to charge forward and double the lead just seconds later.
The win nestles Bologna in 10th place ahead of Sunday's matches and provides a disappointing end to Ancelotti's first campaign in charge of Napoli, who finished comfortably second but never posed a threat to Juventus' charge towards an eighth straight league title.
They were also dumped out of the Champions League at the group stage with qualification in their hands, and were then swatted aside by Arsenal in the Europa League quarter-finals.
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Earlier, relegated Chievo ended a miserable Serie A season in the worst possible fashion when they set an embarrassing points record thanks to a drab goalless draw at also-down Frosinone.
Chievo, who had three points deducted for false accounting before the start of the season, ended the campaign with 17 points following Saturday's non-event at the Stadio Benito Stirpe. That is the lowest in the three-points-for-a-win era since the league returned to 20 teams in 2004.
The Flying Donkeys, who drop down to Serie B after 11 years in the top flight, collected one point less than Pescara did in 2017/18.
However main action is set to take place on Sunday, when Atalanta, Inter Milan, AC Milan and Roma duke it out for the final two Champions League places, while a similarly dramatic day awaits at the bottom of the table.
Serie A's head-to-head tiebreaker format means that 15th placed Fiorentina are in real danger of being relegated alongside Chievo and Frosinone.
The Tuscan outfit are three points ahead of 18th-placed Genoa ahead of the pair's do-or-die clash in Florence -- but have lost five straight in the league and haven't won a game in any competition since mid-February.
Should they lose to Genoa and Udinese, who are level on 40 points with Fiorentina, not lose to Cagliari and 17th-placed Empoli win at Inter, the 'Viola' would go down for the first time since bouncing back from bankruptcy in the early part of this century.
They can also go down if Genoa beat them by two clear goals, Udinese lose to Cagliari and Empoli beat Inter, as they would be overtaken by Empoli and lose a three-way tie-break with Udinese and Genoa.