Nutaku is the only one that can truely detect cheaters.
Good signs of Macro are:

1) Play non-stop for 14 dats or more.
2) Click the same pixel 1000 time in 1 hour.
3) When moving the mouse from spot a to b follow a perfect lines.
4) Play very fast.
5) Do the same thing over and 1000s of times.

I seen games move the screen 1-2 mm per hour(up/down or rigth/left). Real humans can see such slow movements but program that click the same spot will often after some time start to click wrong spot and there by stop working

I seen pop up questions vs macros. At random times normaly 1-2 hours between a question popup. Question are super easy and right answer give a reward so real human gets rewards and are happy Wrong answer gives penalty and a new question. Bots can end up with tons of penanties and if penalti is bigger than benefit from using macro people will just stop using macros without being banned.