It's an interesting quesiton, lots of times you will look at your fleet and look at there's and realistically decide that the ISD isn't worth the effort this game, but when you are looking to take one down what's your favourite way to do it?
Here's some options, pick one or add your own!
1) Use a pair of big ships - What's better than a single ISD...
2) Use a big ship and a medium ship - ISD and Demo Trumps ISD anyday...
3) Use a big ship and a pile of squadrons, Sloan maybe? Rhymer ball? Pile of Y-wings?
4) Use a medium ship combo with squads - Reikan Ace Holes being the obvious choice.
5) Use medium ship killers only - Pair of gladiators? Pair of MC30s?
6) Use a pair of mediums and a horde of squadrons?
7) Piles of little ships? Corvette horde maybe?
I think for me tackling an ISD or equivalent starts with bringing your own big guy and then backing it with a second hitter of some description to straight up overpower the opposition. If I was only running medium or small base ships I reckon it would just got straight into the too hard basket because the risk/reward ratio of trying to use attrition damage isn't worth it. Too many times I've lost a small ship or two only to watch the ISD survive on a card... or even worse, Motti points.
So what's your best way to do it?