How can a referee's decision ever be overturned?

Solution 1:

According to the folks at Kotaku, EA has programmed some level of error into the referees.

Very specific circumstances, like fumbles or sideline catches, may prompt a ref to get a call wrong in order to prompt a potential coach’s challenge.

It's worth noting that these errors (thankfully) don't occur in competitive modes:

Electronic Arts also noted that this human error will not occur in the game’s Competitive play, the default mode for online games and tournaments.

The article doesn't provide a direct source from EA, but they do link to a Quora answer regarding refs/penalties from a former EA employee.

So "long" story short: The refs are programmed to occasionally screw up, in order to make the gameplay more realistic. This also applies to penalties.