Being a professional air traffic controller and working at a busy twin runway airfield somewhere west of London, I always pronounce them "Two and TREE" not "Two and Three". As mentioned before because of my regional accent there is a tendancy to flatten sounds which makes them sometimes difficult to distinguish. This is by no means the worst problem... As mentioned, Niner and Fife are difficult as well, as illustrated a few years ago by having UAL 959 and UAL 955 on the frequency who continually took each others calls despite being told numerous times of the presence of each other and then need to LISTEN CAREFULLY!
Some of the problem as well stems from the fact that a lot of crews are busy and so aren't always 100% focussed on listening to the frequency, and as such tend to mishear things by catching only part of a transmission and then guessing at the rest of it. This has happened to me on so many occasions that I have lost count, and instead of asking for a repeat they stumble over it instead