Well, for one, the American government retained civil and military control over the canal zone until the Carter Administration. This caused a lot of tension in the mid-20th century, as many Panamanians thought that they should be the ones to financially benefit from the massive infrastructure that was constructed in their county.

There were several instances of violence, including the Martyr's Day riots in 1964 in which several dozen people were killed, including a few American soldiers. This was eventually resolved by the Torrijos–Carter Treaties of 1977, which paved the way for complete unqualified Panamanian control of the canal zone by 1999.

There's also the fact that the United States provided support to Panamanian revolutionaries who wished to secede from Colombia (who controlled the territory of present-day Panama) in order to gain more favorable conditions for the acquisition of the site of the canal.

This included sending naval vessels to threaten Colombian seaborne troop movements (so called "gunboat diplomacy") into the rebellious territory. This put a damper on Amero-Colombian relations for quite some time.