Seeing as how I can't be bothered recalling all the moments I had with various boss fights in the past right now, I am just going to point out that I found Slag (Tools of Destruction) and Tachyon (Tools of Destruction) to be the most difficult fights for me to take down. Especially Tachyon, because at least with Slag you can come up with good strategies and level up the right weapons to take him down easily enough.
I do have a dirty little cheat I use on Tachyon that works wonders, though. Just deploy the Visicopter. It may seem mad to those who prefer not to use the device, but experienced users (Ha, experience) may have clicked right now, because the Visicopter has a powerful ability that makes it so whenever you deploy one, Ratchet is completely invincible from any sort of damage until the drone runs out of shots. This is good, because it means you don't need you worry about any of Tachyon's attacks, and you can just stand still and grind him down with this device. But the shots, while quite powerful, are not enough to completely kill him using only this weapon. The device can take down more than half Tachyon's health though, so you could switch from conventional weapons to this device near the mid-point to finish him off. Early on in the fight just use the Groovitron and Death Springs as mentioned by Animovie.