Aside from the obvious fact that being seated next to or right behind the toilet can result in unpleasant odours etc wafting around you, the toilet flush is extremely noisy on most aircraft, and you will find this incessant noise interruption very annoying after several hours of constant repetition. During the darkness / sleep periods you might also tire of the light intrusion every time passengers open the washroom door – and similar to some bulkhead/exit seat positions, you will find that there are often a lot of passengers milling around your seat area as they queue for the washroom.
Most airlines now charge an additional fee to sit in the exit rows, others will allocate at check-in (remarkably some airlines still favour these seats for much taller passengers!). You do get a lot more legroom in an exit seat, but on the downside there are a few points to remember. You will not be allowed to keep any items of hand-luggage (even books etc sometimes) by your seat/footwell area during landing and take-off periods, and as the bins above your seat may be full by the time you realise, you will have to hope for a cooperative cabin crew that will take these items off you at these periods and return them after take-off and landing!
Flying these days is often a huge hassle: You have to get to the airport early to make sure you get through security in time, and then there's the issue of the flight itself. One of the biggest issues related to your comfort and a pleasant trip is where you sit: how much legroom the seat has, how wide it is, and how much overhead bin space there is above you for your carry-on luggage. Other considerations include trying to avoid the middle seat in a group of three, getting your preference for a window or an aisle seat, and sitting close to the front of the section so you can deplane more quickly. If you pick a good seat, it makes the whole journey a lot better.