You can try resetting the form's AcceptButton property based on entering and leaving the GroupBox:
Private Sub GroupBox1_Enter(sender As Object, e As EventArgs) _
Handles GroupBox1.Enter
Me.AcceptButton = Button2
End Sub
Private Sub GroupBox1_Leave(sender As Object, e As EventArgs) _
Handles GroupBox1.Leave
Me.AcceptButton = Button1
End Sub