It's pretty basic. A stock 4Runner simply just does not have enough power to overcome the stock gearing at higher speeds, so what you need to do is keep O/D off to keep the RPM's up, which allows the engine to make more power. Maybe the reason is your 2WD is geared differently than my 4WD.
Say you are doing 90 MPH with O/D on, and you floor it. O/D is not going to let you down shift and you are going to increase your speed much slower than if you had O/D off. It is harder for the 4Runner to pull away from 90 MPH at 3000 RPM (with O/D on, and without a downshift) than it is for it to pull away from 90 MPH at +/-4000 RPM (with O/D off, and the engine at its peak power curve).
Think of it like this: is it easier for a manual transmission car to start in first gear or in fourth gear?