One issue to consider is whether you concentrate your travel on one airline. If so, sometimes getting a co-branded card and spending enough will get you elite qualifying miles. I know this applies to US and DL.

Another issue is whether lounge access is helpful to you. Some relatively pricey cards include lounge access, like Amex Platinum, DL Reserve, and United Club.

Another issue is whether you want to redeem for flights from MKE to RSW. If these are business trips, you probably want to pay for these flights as they would either be reimbursed by your employer or tax-deductible if you're self-employed.

Another issue is amount of overseas travel. One of the best (IMO) travel strategies is to fly enough and make high enough elite status to get system-wide upgrades for international trips that will let you upgrade an overseas ticket to business class. If this is a goal, one of the MQM-qualifying cards would be even more desirable.

In general, I tend to prefer a "generic" card like an Amex Membership Rewards or Chase Sapphire that can transfer to airline partners. This allows you to bank your points until you see an award you want, then transfer the points. I also prefer points cards to cash-back, as I will never really "feel" the cash back I get, but I know for sure when I'm taking a free flight I couldn't have taken otherwise.

I am far from an expert on international award availability, but I get the general impression that Delta is the worst, and that while American is pretty good, if you are going to Europe you sometimes get endplayed into flying BA through England, which has very high surcharges. Amex will give you transferrability to Delta, but also to some Star Alliance carriers where you can book on their own flights or other Star Alliance carriers, including United.

You might also give some consideration to foreign transaction fees if you will be spending a lot overseas. Chase Sapphire Preferred and Amex Platinum have no forex fees.

You said you are spending a lot on business expenses. Depending what categories these are, different cards have different category bonuses. I don't know all the details, but various cards give category bonuses for airfare, all travel, gasoline, groceries, shipping, advertising, and office supplies.

I know I haven't really answered your questions so much as given you targets for further research. But there's a lot to choose from and a lot of variables.