I would make the decision based on what was actually taking the load. If you were using thick wall tubing (1/8" or so) and supported the output shaft with bearings pressed in the tubing, go for it. On the other hand, if the two screws were going into thin walled (1/16th or less) tubing, and were the only thing supporting the gearbox (and the weight of the robot), I'd be a bit more cautious.
We did something similar in 2010, except we didn't direct drive the wheels. In addition to two bolts going through the Toughbox to tubing on either side, we used
this to help support the gearbox.
Keep in mind, like AdamHeard said, if you give us more information, we can give you better advice.