It's easy to go straight for, basically, "all of the frontal assaults that failed with heavy losses", so I prefer looking at the blunders that had the worst strategic consequences. Similar to what Andy just said, I would add the extremely poor placement of Fort Henry, the easy loss of which already guaranteed a massive Confederate retreat coupled with the failure to withdraw from Fort Donelson which could have had decisive consequences at Shiloh. Then of course you have McClellan's retreat from the Virginia Peninsula despite having badly bloodied Lee and his failure to either defeat Lee at Antietam or to pursue and inflict a more decisive defeat, and Hoseman already snatched up my big one, the failure to take Petersburg quickly, which would have more than made up for Cold Harbor as it likely would have meant defeat for Lee in June or July 1864. Kind of makes you wonder what would have happened at Atlanta and elsewhere if that had been the case.