I'm not much help since I'm just starting to plan a trip to the UK myself, but after a quick bit of research for you I think the only airline that does non-stop from PIT to London is BA for now. So you'd want to look at BA and Oneworld alliance partners if non stop is appealing and would prefer to not position to another airport like PHL/JFK/EWR. For giggles I briefly looked at CLE but looks like the same connections as PIT so unless it was a wild savings probably not worth the extra travel.
I have been referring to this blog post to keep track of what fees get charged on award flights for the different options
https://upgradedpoints.com/best-ways-to-fly-to-london-with-points/
I think most of the higher fees are on flights originating from London so if you're making it a one way to London that probably won't be as much of a consideration. We're looking to do a cruise and I'm not sure yet if we'll return from London or add some time at the end to return from another city so I'm keeping it in mind. But, the article runs down some of the majors for awards flights to get you started looking.
I'd also stalk the flights that you can book now to get a rough idea on pricing so you can compare using a flexible currency to using airline points, and the "costs" to acquire.
As a completely made up example, say a round trip flight PIT-LON costs $700 including all fees and is bookable through the Chase UR portal. If you have the CSR that would be 46,666 UR points. That's at least 1 50k sign up bonus per ticket that requires 3-4k of spend to earn (plus AF(s)).
Say this flight is bookable through AA as an award ticket. In a flexible fare bucket (not a web special or something) it'd be 60,000 AA points + $200 in taxes/fees. That's a 60k/65k sign up bonus per ticket that could require up to 4k in spend plus an AF.
Or if the flight you want on AA is a partner flight with surcharges (like BA) then it'd be 60,000 AA + ~$500 in taxes/fees.
Looking at BA flights on BA it'd be 40,000 Avios + ~$650 in taxes/fees. (It'd be more if choosing flights with connections but the fees would be roughly the same) So again, looking at the 50k sign up bonus for 3k in spend plus an AF.
Now you'll have to look at the opportunity for earning those points. Chase has 5 cards with at least 50k UR bonuses, if you're willing to open business cards. There is also opportunities for cross support if you can play in 2 player mode amongst most of those cards. Chase UR can also be transferred to BA if you hold a premium travel card (CSP/CSR/CIP) at 1:1.
AA has two credit card partners, Citi and Barclays. They each have at least one personal AA card and a biz card. You can get cards from both banks, one does not affect the eligibility of the other. So that's 4 worthwhile cards, again, if open to business cards. (To note, AA has been going on a tear shutting down AA rewards accounts for people who took advantage of Citi's incompetence over the last couple years. That's giving it some bad vibes and cautions around these parts. I personally feel that it's not a program to shy away from if you're just starting out and haven't engaged them before, BUT absolutely keep your earnings above board. Now that AA has started this path, I think they'll be more vigilant going forward. So far getting cards from both partner banks is still above board.) Each bank has their pros and cons but if you need a large amount of points you'll probably need both. Citi offers their cards with the first year AF waived but has higher minimum spends to meet the bonus, generally around 4k. Barclays usually offers the bonus on the condition of paying the AF plus a smaller spend requirement, like a single purchase (not sure if that's still available) or $1000.
BA offers a credit card from Chase and typically has a 50k bonus. It also has tiered offers, like right now you can get 100k total if you spend 20k in the first year. As a single card it's not usually very appealing if you need many points but Chase also offers Aer Lingus and Iberia cards which also earn Avios and have the same bonus offers. AFAIK these are all still considered separate cards so you can earn the bonus on each and transfer the Avios to the other programs. Having the BA card allows you to use Avios to pay the taxes/fees on BA award flights, which could be appealing in the right circumstances.
In this completely made up case I might just go with using Chase UR on the portal for minimal OOP cash costs if I'm buying more than 1 ticket. The CSR would be an effective $250 AF but the rest of tickets are covered by points. I might also consider the BA card if I were booking a BA flight since I could use Avios to cover the taxes and again just be out the AF cost if $95 each card. If doing a single ticket I might consider going through AA since the AF is waived on a Citi card and I'd only have about $200 in taxes which is less than the CSR AF. But that wouldn't be on the BA non-stop and it's gets more expensive with multiple tickets so for this scenario I'd put that at the bottom of the pile.
This is not an exhaustive analysis (in fact I'm not totally sure it IS an analysis rather than ramblings
), it gets more complicated when comparing one way flights and even the different CC perks, but this is the kind of path to consider when making plans. I only started down on BA non stop flights for London, if you're comfortable with other options then there's many more paths to consider (like if you prefer Delta you'd be looking at AmEx options instead of Chase) You'll want to compare the options to come up with a primary plan and then pick the next best as a backup and work out the path for both. When you plan far out things can change but if you only plan short term you may not be able to optimize your points use.
If I have the time, I like to work backwards from my preferred activities and and then build a plan to accomplish that. If that plan becomes unfeasible, then I'll rework the trip. You have a start there with your start and end cities so I'd look at one way tickets versus open jaw (multi city) tickets and see which comes out more economical. One way cash tickets are usually prohibitive so an open jaw would make that more comparable to doing one way award tickets - since award tickets are priced out as one ways anyways - for comparisons of the different earning options. Google flights is good to get an idea of who is flying the cities you are traveling so you can drill down into their rewards programs. I hope any of that makes sense!