i'm actually working on a solution for this now. there shouldn't be any issue with the buyers, but ANY sellers would in fact have to maintain some form of hot wallet in order to automate the process.
In p2ptrade protocol, there is no inherent difference between sellers and buyers. Alice announces her offer, Bob then sees her offer and proposes an exchange. Alice might offer with uncolored Bitcoins in exchange for USDcoins, or USDcoins in exchange for uncolored Bitcoins.
If Alice is a market maker of sorts, wanting to perform many trades per day, aiming to earn bid-ask spread, she needs coins in her wallet.
BUT it isn't same as an exchange keeping coins in their hot wallet.
One of major difference is that colored coins allow you to use Hollywood principle: "don't call us, we'll call you".
Basically, your trading machine can be behind a firewall. Or even two firewalls.
You only need to poll p2ptrade order book server from time to time. So you only need to secure HTTP client software and software which processes p2ptrade messages.
This is a very small surface for attack. If you're paranoid, you can implement handler for these protocols in a very defensive style, using programming languages which are regarded as secure (Ada, Haskell, ML...), maybe even use formal verification.
If you follow all security protocols... In order to penetrate through this, attacker will have to penetrate through your firewall(s), then penetrate through security of operating system which has no open ports... Well, good luck with that.
There is a second degree of defense... Let's say you're a market maker and you have 10000 USDcoins and 100 BTC. However, maximum order you're willing to process is 100 USD/1 BTC, and you keep only 1000 USD/10 BTC in your hot wallet.
When hot wallet is exhausted, you receive a notification. Then you can get a log from trading system, get it on flash drive to your secure, air-gaped computer. Analyze log and refill hot wallet as necessary. Then move refilling transactions to trading system...
So basically you keep majority of funds in your secure, air-gaped, encrypted system which might require all kinds of authorization (password, fingerprint scan).
Even if attacker will penetrate through first line defense (which is next to impossible if it is done properly), he only gets 10% of funds.
There is, however, an alternative to this: slow order processing. Market maker might announce his offers and log off. Then log on hour later and process these orders. Potentially, manually...
This requires some changes to protocol, and some reputation system. But it is definitely doable.