To date I have trophied out on the game and it was a blast doing it. the only issue I had was trying to perk out my gernade skills. It was really hard for me to get enemies to drop their gernades so they could take out other foes, along with tossing them back to get them killed. It went against my nature of just running up to them and filling their bodies with lead.
Uber is not that bad really. Just have to take it slow and careful. it also helps when you have all the heath/armor upgrades and perk unlocks. That's how I did it with my game.