Re: is there a scientific rule

The word "harder" has a lot of meanings in the physical context.

If you mean that you have to apply more force vertically downward on the 
rope, than at a 45 degree angle, then that assumption is incorrect.
The force you must apply to one end of a rope wrapped around a pulley with 
a weight on the other end of the rope (in order to lift it) does not 
depend upon the angle upon which you pull it at in reference to the 
pulley/ground.

It might be less "harder" to pull at an angle insofar that you might be 
able to get a better grip on the rope at an angle, or perhaps be in a 
better posture to put your own weight into the downward lifting, or 
perhaps even just walking away with the rope in hand and not using your 
arms to pull it.

[Moderator Note:  Just to add to Gary's answer:  the mechanical advantage
for a fixed pulley will be 1; if you instead made it a moveable pulley, then it
would be 2 (that is, you could apply less force to lift the load than the weight
of the load).  But the really interesting stuff happens when you combine fixed
and moveable pulleys, as shown very nicely at this site. -- RJS]