Tell them I'm from Taco Bell and wish to take them to the slaughter house.
Otherwise it depends on the pony as an Earth Pony could be stopped by a simple gun and decent suit of armor.
A Pegasus's main strength is the ability to fly and use the wind so a good counter would be to use the wind against the Pegasus by either stopping it or stirring it up. Also electricity is very useful against flying things such as wires and anything that can generate a channeled amount of static. Mythical weapons like electro magic, Zeus's lightning bolt, or Thor's hammer.
Now unicorns are a tough foe as magic could be anything depending on the unicorn. One way to defeat magic is having magic of your own that counters their magic. Magic resisting armor or weapons (think deadpool's anti regeneration sword) could be useful. Also having some sort of way to steal or drain magic would help in that kind of situation. Usually magic requires some kind of other godly weapon to kill it. Or you could try to out brute it and just crush it with a meteor or something.