Here's what I am using to base things on:
For the most part you can break even with 20-50 units of cargo on a long haul ship, so operating cost doesn't even factor in to things for my purposes. It might cost 2-3,000 or so to cross the entire map, so the cost is pretty negligible. You can get a good 10-20,000 in revenue for even 100-200 units of cargo, so the profits are easy to attain in that respect. The key is having enough cash to last that long. It takes 5 real life seconds to travel a single tile at 15 km/h which is about ~30 seconds in game time. So to travel 8,000 tiles = 1,000 km (1,800 in operating cost at 1.8 per km), it will take over 60 game hours to make that journey, which is nearly a year long. If your infrastructure to facilitate this trip (stations, depots, etc) costs, say, 1,000/month to maintain, you need 12,000 in cash reserves in order to survive the first year until the first boat arrives to deliver its cargo. Add to this the fact that you will probably need 20-30 convoys in transit in order to have a steady income stream and feed the industry supply/demand requirements and you require a further 50,000 on hand in order to continue building ships to send to sea. So consider having at least 60,000 in cash set to the side in order to support this kind of long distance arrangement. This example highlights how important it is to keep your standing infrastructure monthly cost in mind while building networks -- your boats have to bring in enough revenue to not only offset their operating cost but also offset the high monthly maintenance charges.
Of course, this is only if this is your only route. What I do is mix some long distance, profitable routes, with some short distance lower profit routes. The shorter routes aren't as profitable but they bring in steady cash flow in order to offset the losses from establishing your longer routes. Once the longer routes start delivering their cargo, the profits come in nicely. I'm looking at some very tidy profits coming in the summer in the current game, assuming the crash can be resolved.
EDIT: To address your other point, yes, I have done some simulations of trial routes in solo save games, especially with these recent crashes.