My thoughts:
About crashing/getting hit: well, it happens, but you can minimise the risk and make sure that if it does happen, you are prepared. Wear a helmet if riding on busy roads and pay attention when you are on long rides (it's easy to lose concentration and go into autopilot, which is usually when you veer into the kerb). As for being hit by cars, wear bright clothes, make sure you are lit up like a christmas tree at night (and completely ignore people who say that lights and reflectors are for wimps), and be extra vigilant at junctions and on roads with high speed limits. If you are on a narrow road, don't ride right up next to the kerb, because if your tyres hit the kerb, down you go. Also, this just encourages cars to try and squeeze past you, which is a bad thing. Keep a couple of feet between you and the kerb and if you are blocking traffic - tough, they can wait. If someone really needs to get by or you are obstructing an ambulance or something, just pull off the road and let them by. This stuff is really all just common sense, though. What else - oh yeah, if cycling past a row of parked cars, keep your eyes peeled for people opening doors - imagine a door opening in front of you, and ploughing into its edge at 20mph. Not good. The same goes if you are cycling along next to a pavement with loads of pedestrians on it - they have a nasty habit of stepping out into the road without warning.
Flat tyres are a pain in the neck but not really a major issue. Bring a little pump with you (you can get small ones, about 10" long, which work on both strokes of the handle, and will easily give you the 80psi or so that you need to get home safely), a spare tube or two, and a mini puncture repair kit. I tie the pump to my seatpost with a spare tube and carry the rest of the stuff in my pockets. Practice changing tyres at home, keep the tubes coated with talc to reduce friction, and if your tyres are tough to get off the rims, bring plastic tyre levers. If any of this is unclear to you, ask at a bike shop and they will happily tell you all you need to know. If I am not going to go further than about 3 miles from home (e.g. when I am just hill training), I don't even bother bringing stuff to fix flats. Also, if you only ride on dry roads, you will greatly reduce the chances of getting flats - glass and sharp objects cut rubber much more easily when wet. It's probably a good idea never to ride a road bike in the wet anyway, because you don't want mud and **** in your expensive drivetrain - but that is down to personal preference.
Saddle soreness is one of these tricky things - everyone has a different shape and different preferences, and your riding position of course makes a big difference, so there is no magic answer here that will solve everything. If you have not ridden a bike for a while, then regardless of what you use, your bum will hurt for the first few rides, but that goes away very quickly. After that, you can limit saddle-soreness by investing in a good pair of padded shorts and a good saddle (try to persuade a bike shop to let you test-ride a few - this won't be conclusive because you can't really figure out what works for you until you've used one for quite a while, but it's better than nothing). The Fizik Arione isn't cheap but is getting rave reviews left, right and centre. I use one and I think it's great. Be wary of saddles that have loads of padding - this can seem like a good idea, but in fact saddles with minimal padding are often comfier in the long run, because the weight is taken on your bones, rather than allowing the bones to sink into the saddle, causing pressure to be applied to the soft tissues. Believe me, penile numbness is utterly terrifying ("oh my god where has it gone?!" etc. - you get the idea).
As for your weight, it shouldn't cause any problems but just for reliability and peace of mind, try to avoid bikes with ultra-low spoke count wheels like, erm, the Specialized Allez Comp. Those 16-spoke Shimano wheels look funky and are said to be very fast, but they have a bit of a reputation for being wobbly and bendy at the best of times, so they aren't really recommended for heavier riders. Perhaps your bike shop could swap the wheels out for you, and deduct the cost of the Shimano wheels? Go for standard 32-spoke, 3-crossed wheels, such as Mavic Open Pros laced with quality spokes to Ultegra hubs. They'll be cheap, durable and dead easy to fix in the event that something does go awry. I've test-ridden the Specialized Allez Comp and it's a lovely bike - very solid and stable-feeling, and comfy geometry. Possible alternatives at a similar price point are the Trek 1500 and Bianchi SL3, which reminds me - test ride a bike with a Campagnolo group, just to see if you like it. I was dead set on Shimano but one spin on a Bianchi with a Campag group, and I was converted.
Some miscellaneous stuff about getting into road cycling:
1. Don't be surprised if you find riding your road bike tiring, frustrating and uncomfortable at first. You say you have been doing casual mountain-biking for a while. Well, mountain bikes have a different riding position to road bikes, and you exercise different muscle groups in the two kinds of riding, so being folded in two on a road bike will probably feel awkward, tiring and achy at first. Get your bike shop to fit you properly to the bike, get the saddle, stem and bars set up properly and then just ride and ride and ride - you will get used to it and after a few hundred miles (not nearly as far as it sounds) you will feel perfectly at home on the road bike.
2. Use clipless pedals. They take some getting used to and you will probably fall off a couple of times, but it's well, well worth it. They improve riding in every possible way - they train your legs better, they give you more power, more torque, more control, better balance, a better work-out - they just improve the experience in practically every way possible.
Finally, if you are road biking, losing 40 lbs in a year is dead easy. You could double or even triple that, no problem (of course you, being 6'4" and 240 lbs, can't lose 120lbs without getting something amputated, but you get the idea). Good luck and enjoy yourself!
