Everyone's challenges are different, but for me it's usually fruits being stolen by birds and squirrels, and pests eating up leaves before any of the fruits have been produces.
Only two things have worked for the pests: one is rotating crops. The pests show up, lay eggs in the spot where the plant is, and then they hatch the next season, so I try to plant in different areas each time. This doesn't work for tomatoes, who like being planted in the same spot each year, but I have a different solution for that.
Once I've got leaves coming up, and as soon as I see they're nibbled on, I take a piece of cardboard from a shipping box, and cut it about 6" square. Then on one side, cut up into the middle, and cut a circle about 1 cm in diameter. Twist the cardboard so that you can get it around the plant, and let the plant grow up through the hole. You'd think that 1cm would be large enough for the bugs to get through, or that they'd be able to fly around and above it, but I guess my bugs are just really fucking dumb. It's stopped the nibbling in 100% of the cases I've deployed it, so this is currently my favorite solution.
For the squirrels and birds I use bird netting. I usually stick PVC pipes about 3-4 ft. in height at the corners of my beds, and then drape the netting over them. The sides can be weighted down with stones/heavy objects, or you can tie it to fencing or whatever you have. I do have to move it aside when harvesting or weeding, but it's not a big time sink for me.