Why is setting up partner(s) with God a grave sin, causing all other good deeds useless?     

62-67 of Chapter 39:  

Allah is the Creator of everything and over every thing He is the Guardian. To Him belong the keys of the treasures of the heavens and the earth; and the losers are only those who disbelieve His Revelations. (O Prophet,) say to them, "Ignorant people! Do you bid me worship others than Allah?" (Tell them plainly this because) the Revelation sent to you and to all the Prophets before you has been this: `If you commit shirk, all your works will be rendered vain and you will be among the losers." Therefore, (O Prophet), you should worship only Allah and be among His grateful servants. These people have not recognized the true worth of Allah as His worth should truly be recognized. (As for His Omnipotence) the entire earth on the Day of Resurrection shall be in His grasp and the heavens shall be rolled up in His right hand. Glorified is He and Exalted above what they associate with Him.