#1. Johnny Nitro replaces Chris Benoit due to one of WWE's most tragic incidents
As much as we hate to add this to the list, it's the most significant point, and can't be ignored. The replacement, in this case, happened around the same time of the tragic Benoit family double murder-suicide case.
Chris Benoit was originally set to face CM Punk for the ECW World Championship. While it would have been a dream match in WWE in any period, the actual events that happened were unknown at the time.
Chris Benoit had missed the house shows he was scheduled for, citing a family emergency, and as is the case with WWE the wheel kept spinning. Chris Benoit would be replaced by Johnny Nitro, who went on to defeat CM Punk and become the ECW World Champion in what was considered an upset.
While we could go on about how Johnny Nitro used the title win to change his name and improve his character, it's hard to ignore the tragic circumstances of the replacement.