What strategy can I use to beat Isaac?
As is most things in the game, your items will tell you how you should approach your strategy against Isaac. I've had bomb tears, lazers, rapid fire tears, etc. and took a very different approach each time.
General hints:
For Isaac's first form he shoots 12 radial tears. You are safe just above or below the room's center left/right (see this video). He also shoots retaliatory tears in an arc like the blood tears Monstro shoots, some might go short, some might go over you, so look for the shadows to where to dodge them. I generally just keep spinning in circles around Isaac shooting him and dodge the shadows when necessary.
His second form he shoots homing purple tears and shoots tears when hit. Again, circle around him, dodging tears when necessary.
When he starts spawning the angel babies (3rd form) that's when I usually pull out my consumables. Use your death card, my little unicorn, bombs, etc. Use em if you got em!
Also, since Isaac pauses between active attacks, it's possible to drop bombs around him with relative safety while circling him. This has an added bonus of possibly killing some of the spawned baddies he creates in his 3rd form.
Wiki link: Isaac (Boss)
It's not simple to "make the fight easier", since Isaac
(and ???)
are supposed to be the hardest bosses in the whole game.
You strategy will vary wildly depending on your setup, always be prepared to adapt.
First of all, if you're still struggling to get your first Isaac kill, I suggest you to choose Isaac himself as your character, since the D6 will help you in rerolling the useless items, hopefully into something more useful.
Second, try to complete "The Doctor's Revenge!" challenge, then try to find as many secret rooms as you can. Getting the Epic fetus isn't easy, but it's basically an "I win!" item (remember to shoot with the mouse).
Try to improve your mobility, having a ton of damage and no speed will only get you killed (unless you can one-shot him or have an insane amount of health, it can happen but it completely depends on luck).
If you have a high fire rate prepare yourself for a lot of retaliation shots, a high mobility can help you here (see above).
Generally speaking High damage=Good. As it has already been suggested, in phase 3 drop all the remaining bombs you still have, those little angels can get really annoying if you let them pile up.
The radial shot can be avoided quite easily; be careful with the homing shots (the purple tears), they're fast, but if you keep moving close to the walls, they won't have enough space to turn and follow you.
As a closing suggestion, sadly, I have to tell you that you have to rely on luck: you can make the best run in the world, avoiding everything, only to arrive at Isaac finding out that your damage isn't enough, and being killed just because the fight is gonna take 20 minutes and you'll get tired and make stupid mistakes (yes, it happened to me). Keep fighting, don't lose your patience and finally you'll be victorious!
I chose Cain and abused pills. Since he throws a ton of projectiles, try to use a lot of slot machines so that you can get pretty flies. Anything that will absorb projectiles will help. He doesn't really have anything that pierces, he's just a bullet hell.