Suggested

Tyre rule

Sounds simple but in practice I imagine it would be difficult to programme the checks into the game.

I suppose it would be reasonably easy to provide tick boxes for the host and put checks in place to ensure the main strategy used more than one compound but it leaves an exploit for on-line managers.

So I could set up for a Monaco 50% race - 13SS/13SS/13S in the main strategy to comply with the two compound rule. But during the race I could change my selection to SS for the final pit stop and as a result I race 13SS/13SS/13SS.

It would mean that the simulator would also need to be programmed to check for multiple tyre compounds but ignore the rule if there had been rain at some point of the race.

A penalty during the race is out of question I think, but a time penalty or loosing a set amount of ranks after the race concluded should be possible, the game needs that tyre information to compile the race reports as well. The rain case is a bit more difficult, it could be set that the use of Intermediates or Wets only is OK by the rule regardless of weather, but this relies on the precondition that using them all race in dry conditions just won't work due to wear/performance. 
Another problem would be how the teams with default strategy should be treated.

I was thinking more along the lines of the game enforcing the two tyre rule, not imposing post-race penalties.

Enforcing is even harder to do than a penalty in race. Coming to mind are 3 possibilities. 

First would be checking fuel and if the prediction tells it'll (almost) last to the end of the race and only one compound was used so far that tyre is blocked. But I see problems right away. If cars get lapped it causes problems as those technically don't finish the full race. Then how to handle it if the tyre is chosen first by the manager and then the fuel upped, especially making sure the manager notices that the tyre selected isn't usable anymore. Also probably not feasible due to (programming) effort compared to its use.

Easier to do would be changing the rule that stint one and two have to use different compounds. The downside is more of a limitation of choice of strategies.

Finally there would be an enforced pitstop entering last lap if no two compounds were used so far, but that would be more a penalty than enforcing the rule again. Also possible problems with lapping again but less so as there's way less race remaining (Although in case the car is lapped in pits and the box is before the finish lane that last stint with the second tyre will be a rather short one, if it's after enforcing the tyre fails).

Agreed, hence my comment "Sounds simple but in practice I imagine it would be difficult to programme the checks into the game" in response to Andy's "As simple as that"

Pre race would be relatively simple, do not allow a main strategy to be saved unless there are two compounds selected. It becomes more difficult where a manager has manually over ridden the main strategy and selected the same compound for all stints during the race.

In this situation a penalty would need to be applied. Easiest would be to check the compounds used as the car finishes the race, if only one compound and there has been no rain at any point the offending cars have their result eradicated. In other words it would be as if they'd never run the race.

For those teams where the manager hasn't carried out a pre-race setup, the default main strategies would need to be changed to use two different compounds.

But in any event the point I was trying to make is... it isn't