In my opinion, I think there should be limits on a number of things:
1. Fleet
Currently, if you maintain a good credit standing, you can lease 10,000 aircraft at once. That's absurdly high, even most spamlines don't use that many. The largest airline in the world by fleet (American) has 965 aircraft. They own most, if not all, of their aircraft. RyanAir is the tenth-largest, and although they lease most of their aircraft they still only number 306 of them. There should be an appropriate maximum limit on leases and/or total planes, the largest airlines who attempt realism in AE number about 1,500 aircraft at most.
1b. Fleet Types
A lot of spamlines operate every type of aircraft they can, buying out the whole used market. This leads to the airlines having 20+ different aircraft types (variants not included). The now-merged American has 9 types in use (17 including variants), I think 20 types (variants included) would be a fair amount. Additionally, there should be a limit on how many widebody types an airline can use, even Emirates has only 4 basic types in use (9 including variants). 5 basic types should be the maximum.
2. Hubs
Delta has 13 hubs, the most of any airline. Although this is about as many as even the largest spamlines have, they tend to utilize them much more than most real airlines, having routes to every conceivable destination from them. What I propose here is a limit on hubs, at around 15. Another thing, a lot of spamlines technically should have hubs but do not declare them as such. I think that an airline should be able to have no more than 5 gates at a domestic airport (leased or terminal) before forcing the airline to to/automatically declaring the airport a hub. The existing ten gate lease limit should apply in all airports, regardless of their location relative to the airline. If possible the gate limit might also be changed depending on distance from the airport, due to how they're used (you can lease less gates at an airport 7,000 mi away than one 2,000 mi away, since you have to use much bigger aircraft on the latter).
3. Prices/Competition
There should be a limit on absurdly low prices as well. Take this small airline I have, based in Papatee, Tahiti. On a route between PPT and LAX, 4105 mi away and with a 66Y demand, I have a $380 Y price (from an original of ~$800) and am competing against 2 other US-based airlines on it. I think there should be a limit on how low the price on a route can be set and how many airlines can operate on a route due to demand, most spamlines drastically undercut routes to discourage any competition and flood absurdly small routes to reap profit from them. Additionally, adding onto the last part, there should be a limit on how much over the demand an airline can place its flights. It's fair to serve 450Y on a 300Y route, but it's another thing to serve 700Y on a 140Y route.
Any combination of these three would help solve the problem, and help provide a more enjoyable experience for everyone. If you want to spam, go to Open Worlds, that's why they're there.