When I ride my local routes starting at my house, the last 10 miles are definitely the most challenging because I have to climb hills to get home. Actually the last 2.5 miles are the worst...there are two pretty miserable hills and it's not very fun to deal with them at the end of a ride when I'm tired.

Most other longish rides seem to be hardest for me at the end too. Like today, I rode 51 miles and it was cold (not really that cold, I was just under-dressed) and really windy. After about 40 miles, I was counting down the miles til I got back to the car! I was really ready to be off the bike so those last 10 were miles were killer.