The Welsh actor plays the scientist - whose research on recreating reptilian limb regeneration after he loses his arm in a bomb blast leads to him becoming the Lizard - in the superhero blockbuster and can understand why he becomes the nemesis of Andrew Garfield's Peter and his titular superhero Alter Ego because they are so similar.
He told Clickonline.com: ''There's an emotional correlation between him and Peter Parker. But they're both kind of lost and looking for something, they both don't feel complete. So there's something very moving about these two guys looking for the same thing and then becoming adversaries.
''That's an enduring kind of theme throughout history - brothers falling out and that; it's a theme that repeats itself.
''I do think, obviously I know more about Connors than the other villains, but I do think there's something very, very tragic about him.''
Rhys also believes Dr. Connors' tale is all the more tragic because he turns into the evil Lizard after initially trying to help people.
He said: ''Often the most interesting villains for me are those who want to change the world and want to do good but obviously in the eyes of the good guy it's clumsy or reckless to say the least. So I was interested to see how a man's' passion for his science and his need to do good could turn into rage.''