That's essentially what the B-52 is: an airliner-sized, subsonic jet bomber with a huge capacity and a long range. And apparently they're still in active service. (After 64 years!)

The main downside that I can think of is that you really need air superiority to use them effectively, because they can't outfight, outmaneuver, or run away from any sort of enemy fighter. That's not a big deal against ISIS, but it's no good for prospective conflicts with China or Russia or whatever. Also, modern tactics tend more towards precision strikes rather than massive carpet bombing or, God forbid, nukes.