Why are you guys underestimating Orochimaru & Tsunade? Remember, Minato's Sensei is Jiraiya and is equal footing with the other two as Sannin. If it was a healthy Orochimaru & a prepared Tsunade, i will say this battle would be tough.
Remember, Tsunade is a close range fighter. Not only she can use her insane strength taijutsu in battle, but also, she can use combat medical techniques to aid her. As of now, Minato hasn't shown any long range attack that could give Tsunade disadvantage, only his speed. As seen in the fight with Bee, stabbing him was the way of killing Minato used instead of using ninjutsu. So rasengan & a kunai won't kill Tsunade, hence, Minato being near to her only gives Tsunade an opening for an attack. Also, don't forget that Tsunade is good in seals, so who knows what she's capable of. (Source: Uzumaki & Senju + Medical Specialist) As someone said above, she could level the ground to misplace the Kunais.
As for Orochimaru, I know that If his hands weren't sealed, he could use forbidden devastating jutsus. He's very durable and good at reanimation.
So I'll go for the two Sannins.