Eighth seed Martin Klizan had already seen his tournament end prematurely on Tuesday, but five more members of the ATP 250 event's top eight - including top seed Fabio Fognini - have now followed him out.
In Fognini's defence, his defeat came at the hands of wildcard and defending champion Juan Martin del Potro - the fit-again Argentinian coming from behind to win 4-6 6-2 6-2.
After being outnumbered two breaks to one in the opening set, Del Potro won two games on Fognini's serve in each of the remaining sets to book his place in the quarter-finals.
Fognini's elimination should have opened the door for second seed David Goffin to make a push for the title, but the Belgian squandered his opportunity as he lost 6-3 6-3 to Simone Bolelli in the very next match.
Goffin was unable to get the better of Bolelli's serve, and, after missing to chances to break in the first set, never really got a look-in.
Having seen the top two seeds fall at the first hurdle - the first four seeds enter the competition at the second round - Philipp Kohlschreiber could have been forgiven for being wary heading into his clash with home favourite Bernard Tomic.
And any potential fears were justified as Tomic claimed a 6-3 6-4 win.
Sixth seed Pablo Cuevas and seventh seed Jeremy Chardy were also eliminated on Wednesday at the hands of Mikhail Kukushkin and Gilles Muller respectively.
Julien Benneteau and Leonardo Mayer picked up wins to ensure there will, at least, be two seeds in the last eight. Unfortunately for the pair, they meet each other in the next round.
Benneteau beat Vasek Pospisil 7-6 (7-3) 6-3, while Mayer was a 4-6 6-1 7-6 (7-3) victor against Jerzy Janowicz.
In the day's remaining match, qualifier Viktor Troicki battled to a 4-6 6-3 6-3 victory over Pablo Andujar.