On a plane on her way to Australia, Lucy realizes she can't leave Gru, opens the plane's door and jumps out, using a foldable hang glider to fly back. However, it's impossible to open those doors when a plane is flying at altitude, unless you're Superman or the Hulk.

During their wedding, Gru and Lucy try to kiss, but their long noses comically get in the way. It is stated that they went on 147 dates before getting married though, so shouldn't they have worked out that particular problem by now?

PX-41 makes the mutated purple minions nigh indestructible, which Macho demonstrates by using a variety of weapons on a minion who remains completely unscathed. Macho later uses it to turn himself into a huge purple monster, but Gru takes him down with Lucy's taser lipstick. I would think the mutagen should have made Macho impervious to that weapon as well.